Ya-Li Zhang, Zhen-Su Zhang, Ba-Ping Wu,Dian-Yuan Zhou, PLA Institute for Digestive Diseases, Nanfang Hospital, The First Medical University of PLA, Guangzhou 510515, Guangdong Province, China
Supported by Key University Teacher Funds by the Ministry of Education
Correspondence to: Dr. Ya-Li Zhang, PLA Institute for Digestive Diseases, Nanfang Hospital, Guangzhou 510515, China. zhangyl@fimmu.edu.cn
Telephone: +86-20-85141544
Received 2001-03-05 Accepted 2001-06-25

Abstract
AIM: To review the present studies on early diagnosis of colorectal cancer.

METHODS: The detective rate for early cancer is 1.7%-26.1% based on various statistical data, with much higher detective rate in endoscopy. Since early cancer means invasion involved in the mucosa or submucosa, the diagnosis can only be made when the invasive depth is identified. Pathological tissue materials from both surgical operation or endoscopic resection are suitable for early cancer evaluation.

RESULTS: Incidence of polyp malignancy is 1.4%～20.4%. The various constitutive proportion of polyps may explain the different rates. Malignant incidence is higher in adenomatous polyps, that for villous polyps can reach 21.3%-58.3%. Type II early stage of colorectal carcinoma is rarely reported in China. It is shownd that majority of them were not malignant, most of type IIa being adenoma or hyperplasia, and IIb being inflammatory and IIc might be the isolated ulcers. The occurrence of malignancy of type II is far lower than that of polypoid lesion. In China, the qualitative diagnosis and classification of neoplasm generally adopted the WHO standard, including surgical excision or biopsies. There is impersonal evaluation between colorectal pre-malignancy and cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter is marked with cancer invasion. Diagnosis of early stage colorectal cancer in endoscopy is made with too much caution which made the detective rate much lower. Mass screening for asymptomatic subjects and follow-up for high risk population are mainly used to find the early stage colorectal cancer in China. Fecal occult blood test is also widely made as primary screening test, galactose oxygenase test of rectal mucus (T antigen), fecal occult albumin test are also used. The detective rate of colorectal cancer is 24-36.5 per 105 mass population.

CONCLUSION: Although carcinoma associated antigen in blood or stool, microsatellite DNA instability for high risk familial history, molecular biology technology for stool oncogene or antioncogene, telomerase activity and exfoliative cytological examination for tumor marker, are utilized, none of them is used in mass screening by now.

Zhang YL, Zhang ZS, Wu BP, Zhou DY.Early diagnosis for colorectal cancer in China. World J Gastroenterol 2002;8(1):21-25

INTRODUCTION
The colorectal cancer is one of the most common malignant tumors which threatens the people’s health^[1-3]. The occurrence of colorectal cancer has been rising over the past 3 decades. At present, the colorectal cancer is the second cause of death in western countries, and the forth in China^[4,5]. It is clear that the prognosis of colorectal cancer is related to early diagnosis^[6-8], For instance, the five-year survival after operation of colorectal cancer, diagnosed in early stage, is over 80%, but in the advanced stage it is lower than 40%. So, it is very important to improve the colorectal cancer’s prognosis by means of early diagnosis^[9-13]. Recently, much attention has been paid to early detection for colorectal cancer in China. The popularity of the colonoscopy and the mass screening for colorectal cancer in the population who have no symptoms has raised the rate of the early diagnosis of colorectal cancer greatly. However, the study and progress vary among regions in the country, and there are also misdiagnoses. This paper reviews the present study of early diagnosis of colorectal cancer in China.

THE DETECTIVE RATE OF EARLY STAGE COLORECTAL CANCER IN CHINA
At present, the data of detective rate for early stage colorectal cancer are not perfect, and the detective rate is 1.7%-26.1%, based on various reports (Tabel 1)^[14-20]. The major reason for the different rate is the various statistical data. In virtue of the endoscopy popularity, the early stage of cancers are detected increasingly. Most of them can be treated by non-surgically. So, there are great differences between the endoscopic and the surgical data. For example, 997 cases of colorectal cancer were treated surgically during 1990-1999 in Nan Fang Hospital, 21 cases are in early stage (2.1%), while 1087 cases of colorectal cancer were found from 20 353 colonoscopied cases during the corresponding period, in which, 146 early stage of cancers were identified (13.4%). Because most of early cancers are polyps-like and easy to be resected under endoscopy, the percentage of early stage cancer in surgical samples is low.

Table 1 The detective rate for early stage of colorectal cancer in China

MORPHOLOGY OF EARLY STAGE COLORECTAL CANCER UNDER ENDOSCOPY
There are two types of early colorectal cancer based on the morphological classification under endoscopy. Type I also called protruded or polyps type, can be further grouped as pedunculated(Ip), subpedunculated (Isp) and sessile (Is) superficial type. Type II can be classified as elevated(IIa), flat(IIb) and depressed (with or without protruded )^[6,19]. Since early cancer means invasion involving the mucosa or submucosa, which is not related to the tumor size or special morphology, the diagnosis only can be made when the invasive depth is identified. Pathological tissues from both surgical operation and endoscopic resection are suitable for early cancer evaluation. It is important that early cancer diagnosis can not be made based on the endoscopic biopsy since invasion is not observed.
       Histopathological examination of polyps under endoscopy is a crucial method to detect early cancer in China, and most of them are polyp malignancy^[9,14,21,22]. Generally, polyp formation is mostly involved in the proliferation of mucosa and submucosal tissues. As long as cancerous tissues do not touch upon pedicle, they can attribute to early-stage carcinoma. If pedicle of polyp invasion in colorectal cancer can not be observed for incomplete resection or embedded in the wrong direction, diagnosis of early-stage carcinoma can not be made rashly. Incidence of polyp malignant transformation is 1.4%-20.4% (Table 2). Different result may be from various constitutive proportion of polyps. Malignant incidence is high in adenomatous polyps. In villous polyps, it can reach 21.3%-58.3% according to the documents in China^[23-31]. Moreover, as some adenomatous ingredient are observed by biopsy,some advanced colorectal cancers are diagnosed as polyp malignancy by pathologists. This kind of lesions can not be included in the early-stage carcinoma. In our previous study, 87/127 (68.6%) advanced colorectal carcinoma had residual of adenoma.

Table 2 The malignant transformation rate of polyps in China

Type II early stage of colorectal carcinoma is rarely reported in China. Huang et al first summarized 6304 patients detected by colonoscopy from 1974 to 1996 in a hospital of Beijing^[32], only 36 Type II lesions were discovered, including 31 (86.1%) typeⅡa,4 (11.1%)type Ⅱb and 1 (7%) type Ⅱc. Thirty-two tubular adenomas, 3 villous adenoma and 1 carcinoid were confirmed by histopathological examination,. Only one case was identified as malignancy by follow-up.
       In 137 cases of early stage colorectal cancer detected in Nanfang Hospital from 1990 to 1999, 95.6% were polypoid type, only 6 cases were considered as type II(4.4%)(Table 3). We also analyzed the histopathological features of 186 cases of type II lesions, only 3.2% were diagnosed as early stage carcinoma(Table 4). It indicated that the majority of so-called type II cancer under endoscopy were not real malignancy. Most of type IIa were adenoma or hyperplasia polyps, and most of type IIb were inflammatory changes of mucosa. A large number of type IIc cases might be the isolated ulcers. The occurrence of malignancy of type II is far lower than that of polypoid lesion.

Table 3 Morphology of 137 cases of early stage colorectal cancer under endoscopy

Table 4 Histopathology of 186 cases of type II lesion

THE DIAGNOSTIC STANDARD FOR EARLY STAGE OF COLORECTAL CANCER
In China, the qualitative diagnosis and classification of neoplasm generally adopted the WHO standard for both surgical excision and biopsies^[17,33]. The evaluation is objective between colorectal pre-malignancy and cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter is marked with cancer invasion^[34-37]. Although pathologists hold different opinions about the classification of dysplasia, it could be classified generally into 3 grades. The simpliest classification depends on the ratio of dysplasia karyon in epithelium. Mild dysplasia indicates the crowding nuclei limited within 1/2 depth of epithelium in basement, moderate dysplasia means that atypical nuclei occupied more than 1/2 epithelium, and severe dysplasia refers to the atypical nuclei occupying the whole epithelium with integrated basement. The essential difference between dysplasia and malignancy is invasion. The malignancy is manifested by the destroyed basement, and sporadical dysplasia glands. It is called intra-mucosal cancer if the cancer cell invasion limited within the mucosa. If the cancer destroyed mucosal muscle into submucosa, it is called sub-mucosal cancer. These two types are generally designated as early stage cancer. From the literature reviews, we found that the diagnosis of early stage colorectal cancer in China is made with much cautions under endoscopy. On the one hand, pathologic diagnosis generally adopted the WHO standard, which depends on the invasion, and sometimes it is difficult to observe the invasion on biopsy sections. On the other hand, patients always feel panic to cancer, once the colorectal cancer is diagnosed, they would rather choose surgical operation than endoscopic resection. Besides, they often require consultation of the pathological sections, if diagnostic standard is different, this may cause the psychological pressure to the pathologic doctors in different regions.
       In European countries, colorectal cancer is the most common malignant tumor of digestive tract. But the diagnositic rate of early cancer is usually reported less than 9%. In Japan, the diagnostic rate of early stage of cancer detected by endoscopy is 17%-53%. The cases of early stage cancer reported in China is the same as in European countries but far lower than in Japan^[14-20]. Schlemper RJ et al compared the differences in pathological diagnosis of early carcinoma from strippling or surgically resected specimens of colonic mucosa between Japan and Europe-America^[34]. It was found that 4 cancer cases were diagnosed by Japanese pathologists in 11 adenoma with mild dysplasia based on European-American standard. This is because Japanese pathologists emphasize the nuclei dysplasia and gland structural change evaluating malignancy^[37] , but pathologists in China usually take above changes as markers of pre-malignancy.

DETECTION FOR EARLY STAGE OF COLORECTAL CANCER
Mass screening for asymptomatic subjects and follow-up for high risk population are the major ways to find the early stage of colorectal cancer in China^[38-42]. High risk factors are old age, histories of colorectal polyps, familial history of cancer and some colorectal related positive tests^[43-51]. Since mass screening for asymptomatic population need a large amount of work, and exact diagnosis must depend on endoscopical and histopathological examination, screening test has been paid much attention. So far, fecal occult blood test is widely used as primary screening test in China^[52-55]. Other screening tests include galactose oxygenase test of rectal mucus(T antigen)^[56-60] , and fecal occult albumin test^[61,62] . If the screening tests appear positive, colonoscopy is then taken. Although carcinoma associated antigen in blood or stool^[63-81], microsatellite DNA instability for high risk familial history^[82-86], molecular biology technology for stool oncogene or antioncogene^[87-99], telomerase activity^[100-104] and exfoliative cytological examination^[105,107] have been used for tumor marker, none of them is used in mass screening.
       There are some excellent work reported in China on mass screening for colorectal cancer. Most of them are based on immune fecal occult blood test(Table 5)^[54,55,62]. In mass screening(age above 35 years), the occurrence of colorectal cancer is 24-36 per 10⁵ population.

Table 5 Mass screening for colorectal cancer in asymptomatic population

Tantigen detection in rectal mucus is also used in some mass screenings^{[57-60,108,109]}. In 3820 asymptomatic population, the positive rate of T antigen is 9.1%, among them, 2 cases of early cancer and 28 cases of adenoma were identified. The detective rate of pathologic change is 12.7%. It is shown that T antigen test is not specific for colorectal examination. In 103 cases of T antigen positive subjects,85 cases were found without any lesion under colonoscopy. The sensitivity is not better than that of feces occult blood examination^[110-114].Since screening tests used so far are not specific for colorectal detection, there are some misdiagnoses either by feces occu1t blood examination or rectal mucous T antigen test. To improve the detective rate of the early stage cancer,it is suggested that combined complementary screening should be taken. Zhejiang University School of Medicine optimized the screening protocol for colorectal cancer among a high-incidence population^[113]. Through increasing the cases for colonoscopy follow-up, the detective rate of early cancer was increased. Beijing General Hospital reported that by combined test of sequencial fecal occult blood and albumin in the screening of colorectal neoplasma, 3 cases of carcinoma were found from 883 positive asymptomatic subjects^[114]. The Nanfang Hospital recommended the complementary schemes by combining occult blood and T antigen detection. In 5 cases of colorectal cancer, which were found by colonoscopy in 2832 asymtomatic subjects, 3 were positive in feces occult blood examination and 2 in T antigen test. The missed cases will be reduced if complementary screening was taken^[13]. Our study showed that the mass screening can reduce the colorectal occurrence(Table 6)^[113].

FUTURE STUDY IN EARLY DIAGNOSIS FOR COLORECTAL CANCER
It is definite that asymtomatic mass screening is the important way to identify the early cancer. Because of the poor specificity of screening test,and the high cost,it is difficult to popularize. Target screening will be highlighted. In 1992, Sidransky et al first extracted DNA successfully from feces and reported ras gene variation with Southern-Blot^[116]. It is considered an effective screening for colorectal cancer in the 21st century. PCR-SSCP technology has a high sensitivity, good specificity and easy manipulation. Gene mutation such as P53, ras, c-erbB-2, APC and MCC was identified in feces(Table 7)^{[94-96,117,118]}. Since no specific gene mutation is found in colorectal cases, the detective rate by molecular technique is low. Though combined genes detection can enhance the screening rate, it is too complex and expensive.

Table 6 The follow-up results in 3,641 cases of asymtomatic population

Table 7 Gene mutation analysis in colorectal cancer stool(Nanfang Hospital)

Analysis of gene offers possibility and practical significance for detecting high risk population. For example, HNPCC generally represents the microsatellite DNA instability and characteristic DNA mismatch repair gene. Therefore, detecting MIN and DNA mismatch repair gene may identify some high risk population with cancer familial predisposition^[119-122]. We analyzed 46 cases of colorectal carcinoma for MIN, and found 14 cases of MIN positive patients, 12 of them with familial predisposition (85.7%). It is suggested that MIN might reflect colorectal carcinoma with familial predisposition in some extent.

REFERENCES
1     Zhang YL, Nie J, Zhou J, Guo W, Guan CP, Zhou DY. Incidence and geographical features of colorectal cancer in patients 
       under 30 years of age in china. Zhonghua Xiaohua Neijing Zazhi 1997;14:11-14
2     Zhang ZS, Zhang YL. Progress in research of colorectal cancer in China. Shijie Huaren Xiaohua Zazhi 2001;9:489-494
3     Wang SH, Zheng YQ. A clinicopathologic analysis of 354 cases of large intestinal cancer in western Hunan.
       Xin Xiaohuabingxue Zazhi 1996;4:325-326
4     Jing F, Zhou SZ, Tao YF, Fang RY, Xiang YB, Shun L, Gao YT. Cancer incidence trend in Shanghai 1972-1994.
       Zhongliu 1999;19:255-258
5     Yu JP, Dong WG. Current situation about early diagnosis of cancer of large intestine. Shijie Huaren Xiaohua Zazhi
       1999;7:553-554
6     Li GY, Lu YM, Chen FL, Gong JZ. Current situation about diagnosis and treatment of early colorectal cancer.
       Huaren Xiaohua Zazhi 1998; 6:377-382
7     Zhang Y. Guwai Yixue. Advances of diagnosis and treatment of early colorectal cancer. Zhongliuxue Fengzhe
       1999; 26: 114-118
8     Xiao XW. The value of selective chemoembolization in the treatment of hepatiometastases in colorectal carcinoma.
       World J Gastroenterol 1998;4(Suppl 2):38-41
9     Jia XD, Han C. Chemoprevention of tea on colorectal cancer induced by dimethylhydrazine in Wistar rats.
       World J Gastroenterol 2000;6:699-703
10   Feng FC, Zhang YL. Canceration and endoscope treament of large intestine polys. Zhongguo Shiyong Neike Zazhi
       1996;16: 390-392
11   Sheng J, Zhang ZZ, Mo SJ, Liu SY, Wang YL. Endoscopic diagnosis and therapy for early colorectal cancer. Zhonghua 
       Xiaohua Neijing Zazhi 1998; 15: 297-298
12   Cheng FQ, Du H, Zhu C, Jiang H, Wang HZ, Liu SY. Endoscopic diagnosis and therapy for early colorectal cancer: 
       report of 63 cases. Zhonghua Xiaohua Neijing Zazhi 1998; 15: 94-96
13   Zhou DY, Feng FC, Zhang YL, Lai ZS. Study on combination mass screening protocol for colorectal cancer. Zhonghua
       Neijing Zazhi 1994;33:367-369
14   Lu YM, Gu F, Lin SR, Zhu ZM. Significance of clinical screening colonoscopy and colonoscopic polypectomy with
       pathology in diagnosis of early colon cancer. Zhonghua Xiaohua Neijing Zazhi 1997; 14: 222-224
15   Ni PY, Qu HT. Summary of five years follow up colonoscopy on patients with colorectal polyps and cancer.
       Zhongguo Neijing Zazhi 1997; 3: 1-2
16   Yang YX, Li HB, Liu FS, Zhu XD, Zhang YR, Li XL, Xu QX. Preliminary approach of the relationship between colorectal 
       polyps and carcinoma:analysis to 2,237 cases. Zhongguo Neijing Zazhi 1997; 3: 17-18
17   Zhang YL. The diagnosis standard of endoscopic biopsy for colorectal cancer. Zhonghua Xiaohua Neijing Zazhi
       2001; 18: 135-138
18   Cai BY, Yu DY, Wang Y, Gong BQ, Ma B. The clinical pathological analysis of 1058 cases of colon carcinoma. Qiqihaer
       Yixueyuan Xuebao 1999; 20: 5-6
19   Zeng XJ, Guo RD, Guo PC. A Clinical Analuses of 300 Cases of Carcinoma of the Large Intestine. Fujian Yiyao Zazhi
       1996;18:13-15
20   Shun CJ, Yao Q, Xu JZ, Yu BM. Detection of early large intestine cancer during clinical symptomatic inspection: clinical
       and pathological characteristics. Zhongliu 1998; 18: 49-51
21   Zhang YL. Canceration and endoscope biopsy diagnosis of large intestine polys. Zhonghua Xiaohua Neijing Zazhi
       1999;16:188-200
22   Zhou DY, Zhang YC, Zhang YL, Feng HC, Hu Q, Xiao GS. Study on anaplasia potentiality of colorectal adenoma. An 
       analysis of 611 adenomas by endoscope biopsy. Zhongguo Guangdian Yixue Zazhi 1992;1:166-169
23   Cai KY, Huang SZ, Yu XB, Yu JP. An analysis of follow up colonoscopy on 216 aged patients with colorectal polyps. Fubu
       Waike 2000; 13: 105-106
24   Zhang B, Zhen YG, Zhang DH. The clinical pathological features of colorectal polyps by colonoscope management in 
       2000 cases. Zhongguo Shiyong Waike Zazhi 1999; 19: 661-662
25   Sheng LJ, Feng SZ, Zhang L, Pu P. Pathological analysis of 533 cases of large bowel polyps. Yunnan Yiyao
       1995; 16: 267-268
26   Zu C, Zhang JP, Zhang ZQ, Zhao DH. Treatment of large bowel polyps in elderly people with over five years’ follow-up.
       Zhonghua Xiaohua Zazhi 1995; 15: 198-199
27   Zu MQ. Endoscopic Excision of Colonic Polyps. A report of 456 cases. Zhongguo Zhongliu Linchuang 1995; 22: 334-337
28   Wang ZX, Xu DP, Zhou HZ, Lei PS, Cheng SZ. An analysis of canceration of 53 large intestine polys. Zhongliu Fangzhi
       Yanjiu 1994; 21: 236-238
29   Zhang HZ, Tian HY, Xu JH. Clinical analysis of 321 cases of colorectal polyps. Shiyong Zhongliu Zazhi 1994; 9: 30-31
30   Zhang ZY, Pan LN, Wu HX, Li SY. Relation of colorectal polyps and colorectal cancer.A report of 494 cases. Neijing
       1994; 11: 1-2
31   Gao WD, Yao LQ, Zhou PH, Gu SH.Treatment on canceration colorectal adenomas by colonscope. Zhonghua Neijing 
       Zazhi 1996; 2: 42-43
32   Han Y, Li SY. Diagnosis and treatment on early colorectal neoplasmas of type flat and concave by endoscopy. Zhonghua
       Neijing Zazhi 1997; 3: 39-41
33   Zhang YL. The dysplasia of colorectal adenoma. In: Zhang YL eds. Colorectal cancer: Basic and clinical research.
       Shanghai Sci Press 1999: 13-15
34   Schlemper RJ,Itabashi M, Kato Y, Lewin KJ, Riddell RH, Shimoda T, Sipponen P, Stolte M, Watanabe H.
       Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma.
       Cancer 1998; 82: 60-69
35   Schlemper RJ, Borchard F, Dixon MF, Koike M, Mueller J, Stolte M, Watanabe H. International comparability
       of the pathological diagnosis for early cancer of the digestive tract: Munich meeting. J Gastroenterol
       2000; 35(Suppl 12):102-110
36   Riddell RH. East meets West: what is early cancer Can J Gastroenterol 1999;13:495-497
37   Lauwers GY, Shimizu M, Correa P, Riddell RH, Kato Y, Lewin KJ, Yamabe H, Sheahan DG, Lewin D, Sipponen P, 
       Kubilis PS, Watanabe H. Evaluation of gastric biopsies for neoplasia: differences between Japanese and Western 
       pathologists. Am J Surg Pathol 1999; 23: 511-518
38   Chen K, Jiao DA, Zheng S, Zhou L, Yu H, Yuan YC, Yao KY, Ma XY, Zhang Y. Diagnostic value of fecal occult blood testing
       for screening colorectal cancer. China Natl J New Gastroenterol 1997;3:166-168
39   Zhou DY, Feng FC, Zhang YL. Route of early diagnosis on colorectal cancer. Zhonghua Xiaohua Zazhi 1992;12:319-321
40   Zhou DY, Zhang YL. Progress on biologic characteristics and early diagnosis of colorectal cancer. Guowai Yixue: Xiaohua
       Jibing Fengce 1992;1:17-18
41   Zhang YL, Zhou DY, Zhang WD, Lai ZS. Speculation on early diagnosis of colorectal cancer. Yixue Yu Zhexue 
       1993:43-44
42   Zhang YL, Zhou DY. Prophylactic and therapeutic strategy of colorectal cancer. Weichangbingxue He Ganchangbingxue
       Zazhi 1994;3:241-243
43   Xu SB, Zhang WX, Wang LL. Expression of antigen a new tumor marker Sc6 byimmunohistochemical method.
       Xin Xiaohuabingxue Zazhi 1994;2(Suppl 2):49-50
44   Feng FC, Huang W, Zhou DY, Zhang YL, Lai ZS. Study on detection of cancer associated antigen in serum and feces by
       monoclonal antibodies against human colorectal cancer. Xin Xiaohuabingxue Zazhi 1995;3:36-38
45   Chen B, Zhou SJ, Fan DM. Establishment of a quick ConA-mAb-LISA for detection of serum MC3-Ag, a novel
       colorectal cancer-associated antigen. Xin Xiaohuabingxue Zazhi 1995;3(Suppl 4):12-13
46   Luo YH, Fang DC, Lu R, Liu FX, Liang ZY, Liu WW, Men RP, Zhou ZC. Heterozygosity loss at the APC/MCC locus in 
       colorectal cancer. Xin Xiaohuabingxue Zazhi 1996;4:309-311
47   Zhuang XQ, Yuan SZ, Wang XH, Lai RQ, Luo ZQ. Expression and prognostic significance of EGF receptor and 
       proliferating cell nuclear antigen in colorectal cancer. Xin Xiaohuabingxue Zazhi 1996;4:483-484
48   Liu Y, Li QM, Lu MZ. Expressions of nm23-H1, p53 and PCNA in human colorectal carcinoma tissues. Xin Xiaohuabingxue
       Zazhi 1997;5:431-432
49   Zhao J, Pan X, Yin GP, Shan LC, Wang CL. Peripheral blood CD44 contents in 26 patients with colorectal cancer.
       Xin Xiaohuabingxue Zazhi 1997;5:510-511
50   Feng FC, Huang W, Zhang YL, Wang JD, Zhou DY. Clinical significance of serum sIL-2R and TNF in patients with 
       colorectal carcinoma. Xin Xiaohuabingxue Zazhi 1997;5:567-568
51   Qiu SL, Huang JQ. Significance of CD44 gene products for colorectal carcinoma diagnosis and prognosis evaluation.
       Xin Xiaohuabingxue Zazhi 1997;5(Suppl 6):32-33
52   Zhang YL, Zhou DY, Lai ZS. Evaluation of immunological fecal occult blood test for colorectal tumor by specific antibody
       coated staphylococcal protein A coagglutination. J Med Coll PLA 1992; 7:382-358
53   Yu SP, Zheng SJ, Zhou HY. Evaluation of colorectal carcinoma screening with fecal monoclonal antibody.
       World J Gastroenterol 1998;4(Suppl 2):9-11
54   Chen K, Jiao DA, Zheng S, Zhou L, Yu H, Yuan YC, Yao KY, Ma XY, Zhang Y. Diagnostic value of fecal occult blood 
       testing for screening colorectal cancer. China Natl J New Gastroenterol 1997;3:166-168
55   Zhu WX. Comparative fecal occult blood test with the kit of RPHA-Z and RPHA-T. Zhonghua Yixue Zazhi 1987: 673-674
56   Zhou DY, Zhang YL, Nai ZS. A study on the screening of large intestinal carcinoma by reactum mucus T-antigen
       method. Zhonghua Xiaohua Zazhi 1991;11:261-262
57   Xu SY, Lin GJ, Lu Y. Clinical significance of T-antigen in the premalignant condition of colorectal cancer.
       Zhonghua Xiaohua Neijing Zazhi 1998; 15: 285-288
58   Li DB, Wang HB. Application of T-antigen detective kit in screening colorectal cancer.
       Zhongguo Gangchangbing Zazhi 1998; 18: 27-28
59   Lu Y, Xu SY, Wang QY, Li ZM. Determination of T-antigen in large intestinal mucus by galactose oxidase method. 
       Zhonghua Yixue Jianyan Zazhi 1995; 18: 133-135
60   Tan J, Zhang Q, Fang XZ, Kan AP, Cai XL, Zhang SM, Zhang L, Zhang SH. Clinical significance of galactose oxidase-
       schiff reaction in the detection of carcinoma and precancerous lesions of large intestine. Zhonghua Zhongliu Zazhi 
       1997; 19: 157-159
61   Wang ZH. Mass screening for colorectal cancer by semi-quantum testing fecal occult albumin. Zhongguo Lingchuang
       Mianyixue Zazhi 1993: 39-42
62   Wang ZH, Li SY, Cheng ZM. Preparation of rabbit anti-human immuno-carboxylate and its application in screening of 
       colorectal tumor. Zhongguo Zhongliu Lingchuang 1999; 26: 450-452
63   Feng FC, Huang W, Zhong DY, Zhang YL. Study on detection of cancer associated antigen in serum and feces by
       monoclonal antibodies against human colorectal cancer. Xingxiaohuabing Zazhi 1995;3:36-38
64   Hu JY, Su JZ, Pi ZM, Zhu JG, Zhou GH, Sun QB. Radioimmunoimaging of colorectal cancer using 99mTc labeled 
       monoclonal antibody. World J Gastroenterol 1998;4:303-306
65   Fang DC, Luo YH, Lu R, Liu WW, Lui FX, Liang ZY. Loss of heterozygosity at APC, MCC and DCC genetic loci in 
       colorectal cancers. China Natl J New Gastroenterol 1995;1:21-24
66   Zhao CH, Jiang CY, Zhang YY, Liu XX, Luo DC, Zhang XT, Lin YQ. Analysis of LDH activities and its isoenzyme patterns
       in colorectal cancer tissues. China Natl J New Gastroenterol 1997;3:41-42
67   Wu GJ, Shan XN, Li MF, Shi SL, Zheng QP, Yu L, Zhao SY. A preliminary study on the loss of heterozygosity at 17p13 
       in gastric and colorectal cancers. China Natl J New Gastroenterol 1997;3:160-162
68   Zhang J, Lai MD, Chen J. Methylation status of p16 gene in colorectal carcinoma and normal colonic mucosa.
       World J Gastroenterol 1999;5:451-454
69   Xu QW, Li YS, Zhu HG. Relationship between expression P53 protein, PCNA and CEA in colorectal cancer and lymph 
       node metastasis. World J Gastroenterol 1998;4:218-219
70   Cai Q, Lu HF, Sun MH, Du X, Fan YZ, Shi DR. Expression of two CD44 variant proteins (v3 and v6) in human colorectal
       carcinoma and its relevance for prognosis. World J Gastroenterol 2000;6(Suppl 3):75
71   He SW, Shen KQ, He YJ, Xie B, Zhao YM. Regulatory effect and mechanism of gastrin and its antagonists on colorectal
       carcinoma. World J Gastroenterol 1999;5:408-416
72   He Y, Zhou J, Wu JS, Dou KF. Inhibitory effects of EGFR antisense oligodeoxynucleotide in human colorectal cancer cell 
       line. World J Gastroenterol 2000;6:747-749
73   Jiang CP, Chen YQ, Zhu JW, Shen HX, Yu X. Immunohistochemical study of gastrin in colorectal carcinoma tissues and 
       its adjacent mucosa. China Natl J New Gastroenterol 1997;3:84-86
74   Chen DW, Wang YH, Chen XY, Wang Q, Gao H. Clinical significance of immunohistochemical study of P53 protein in 
       colorectal carcinoma. China Natl J New Gastroenterol 1996;2:25-26
75   Hu JY, Wang S, Zhu JG, Zhou GH, Sun QB. Expression of B7 costimulation molecules by colorectal cancer cells reduces
       tumorigenicity and induces antitumor immunity. World J Gastroenterol 1999;5:147-151
76   Feng S, Song JD. Determination of βglucuronidase in human colorectal carcinoma cell lines. China Natl J New
       Gastroenterol 1997;3:251-252
77   Hu JY, Su JZ, Pi ZM, Zhu JG, Zhou GH, Sun QB. Radioimmunoimaging of colorectal cancer using 99mTc labeled 
       monoclonal antibody. World J Gastroenterol 1998;4:303-306
78   Zhou ZF, Yuan SZ. Prognostic value of silver stained nucleolar organizer regions in colorectal carcinoma.
       China Natl J New Gastroenterol 1995;1:43-47
79   Xu YH, Song JD. Expression of tumor associated antigen-LEA in pre-malignent and malignent lesiones of colorectal 
       mucosa. Shijie Huaren Xiaohua Zazhi 1999; 7: 992
80   Xu SP, Zheng SJ, Zhou HY, Guo XL. Colorectal cancer mass screening by cancer associated monoclone antibody in
       feces. Zhonghua Xiaohua Zazhi 1998; 18: 216-217
81   Wu BP, Zhang YL, Zhang ZS, Zhang LL, Guo W, Zhou DY. Microsatellite instability, MMR gene expression in colorectal 
       cancer with famillial predisposition. Zhonghua Liuxingbingxue Zazhi 1998;19:331
82   Wang YP, Waltraut F, Peter P. Analysis of hMLH1and hMSH2 gene mutation in herediatary non-polyposis colorectal
       cancer. Zhonghuayixue Yichuanxue Zazhi 1998; 15: 333-336
83   Wu BP, Zhang YL, Zhou DY, Gao CF, Lai ZS. Microsatellite instability, MMR gene expression and proliferation kinetics in
       colorectal cancer with famillial predisposition. World J Gastroenterol 2000;6:902-905
84   Zhang LL,Zhang ZS,Zhang YL,Wu BP,Guo W,Liu XX,Zhou DY.Microsatellite instability in multiple primary colorectal 
       cancers. Shijie Huaren Xiaohua Zazhi 1999;7:397-399
85   Capozzi E, Della Puppa L, Fornasarig M, Pedroni M, Boiocchi M, Viel A. Evaluation of the replication error phenotype in 
       relation to molecular and clinicopathological features in hereditary and early onset colorectal cancer. Eur J Cancer
       1999; 35:289-295
86   Lin H, Lin JY, Zhang YL, Zhang ZS, Zhou MY, Zhou DY. The detection of the mutation of APC gene in the stool of the 
       patients with sporadic colorectal carcinoma. Zhonghua Xiaohua Zazhi 2000;20:60-61
87   Ji DJ, Cao Y, Zhang YL, Jiang P, Yu N, Feng FC, Zhou DY. Synchronous studies on variations of p53 gene transcriptions 
       and expressions in colorectal carcinomas HT-29 and Lovo cell lines. Shijie Huaren Xiaohua Zazhi 2000;8:77-79
88   Zhen S, Cai YH, Chao J, Zhen L, Mo YQ, Zhang YM, Geng LY, Shi ZZ, Gu JR. Colorectal cancer associated gene analysis 
       by SSH technique. Zhonghua Yixue Zazhi 1997; 77: 256-259
89   Mo YQ, Zhen L, Cai XH, Chao J, Zhu LJ, Zhen S. Expression of new cancer associated gene - HSU 17714 in colorectal 
       cancer and other malignent tumors. Zhongguo Zhongliu Linchuang 1997; 24: 504-508
90   Li M, Wang B, Yu BM, Zhen MH. Relationship between p53 gene mutation and prognosis in colorectal cancer.
       Shijie Huaren Xiaohua Zazhi 1999;7:425-426
91   Zhuan XQ, Lai RQ, Sun GH, Wang XH, Yuan SZ. The expression of p53 protein and PCNA in colorectal tumors.
       Shijie Huaren Xiaohua Zazhi 1999;7:616
92   Shen XB, Zhang XC, Mei LX, Zhao XM, Hu JG.The signification of the expression of nm23/NDPK and p53 in colorectal 
       cancer. Shijie Huaren Xiaohua Zazhi 1999;7:809-810
93   Lin H, Lin JY, Zhang YL, Zhang ZS, Zhou MY, Zhou DY. The detection of the mutation of APC gene in the stool of the 
       patients with sporadic colorectal carcinoma. Zhonghua Xiaohua Zazhi 2000; 20: 60-61
94   Gan YB, Cai XH, Zheng S. Detection of Ki-ras gene mutations in tumor tissues and stools of patients with colorectal
       carcinoma. Zhejiang Yike Daoxue Xuebao 1995; 24: 241-247
95   Luo CY, Li SY, Zhu XG. The detection of the rearrangements of bcl-2 gene in the cancer tissues and the stool of the 
       patients with colorectal carcinoma by semi-nest PCR. Zhonghua Shiyan Waike Zazhi 1999;16: 197-198
96   Cao GW, Qi ZT, Pan X, Zhang XQ, Miao XH, Feng Y, Lu XH, Kuriyama S, Du P. Gene therapy for human colorectal 
       carcinoma using human CEA promoter controled bacterial ADPibosylating toxin genes human CEA: PEA & DTA gene 
       transfer. World J Gastroenterol 1998;4:388-391
97   Xu CT, Pan BR. The study of gene change in colorectal tumors. Huaren Xiaohua Zazhi 1998;6:58-60
98   Yu BM, Zhao R. The recent study on molocularbiology in colorectal cancer. Shijie Huaren Xiaohua Zazhi
       1999;7:173-175
99   Liu BY, Sun ZL, Pan SW, Chui DX, Yuan XJ, Li D, Lei YF, Wang S. Gene expression and early diagnosis in colorectal 
       cancer. Shijie Huaren Xiaohua Zazhi 2000; 8: 43-44
100  Sun ZJ, Zhang YL, Zhang ZS, Guo W, Zhou DY. Study on activity of telomerase in colorectal cancer screening.
       Zhonghua Liuxingbingxue Zazhi 1998;19:327
101  Jiang CY, Ding K, Liu XX, Zhao CH, Zhu S. Study on histoenzymes markers in colorectal cancer.
       Zhongguo Zhongxiyi Jiehe Waike Zazhi 1998; 4: 336-339
102  Wang W, Luo HS, Yu BP. Telomerase and colorectal cancer. Shijie Huaren Xiaohua Zazhi 2000; 8: 800-802
103  Cuo SL,Huang JQ, Wang YF, Peng ZH. Telomerase analysis in pre-malignent and malignern tumors in colon.
       Huaren Xiaohua Zazhi 1998; 6: 992-993
104  Wu XW, Li SY, Wang ZH, Wu X, Cheng ZM, Wu ZT. The evaluation of colonic exfoliative cell for the screening of 
       colorectal cancer. Aizheng 1997; 16: 386-387
105  Fan RY, Li SR, Wu X, Wu ZT, Cheng ZM, Deng YJ, Chao JB, Zhang HG. The expression of telomerase in exfoliate cells of
       colorectal cancer. Shijie Huaren Xiaohua Zazhi 2000; 8: 814-815
106  Li J, Li SR, Cao JB, Gao G. Laser-induced fluorescence spectrum of colon cancer in vivo. Shijie Huaren Xiaohua Zazhi
       1999;7:164-165
107  Luo DC, Dai HJ, Ni YZ, Ci W. A study on the screening of large intestinal carcinoma by t-antigen monoclonal antibody
       method. Zhongguo Aizheng Zazhi 1998; 8: 256-257
108  Liu SC, Bai X, Wei YG, Wang ZL. Reresearch of galactose oxidase in screening carcinoma of the large intestine.
       Huaren Xiaohua Zazh 1998; 6: 990-991
109  Zhou DY, Feng FC, Zhang YL, Lai ZS. Comparative analysis of detecting rectum mucus T-antigen and Immuno-fecal 
       occult blood test in screening colorectal cancer. Chinese Med J 1993;106:739-742
110  Zhou DY, Feng FC, Pan DS, Lai ZS, Zhang WD, Zhang YL, Wan TM, Li LB, Xu GL, Zhou D. Evaluation of optimized
       screening protocol for colorectal cancer amonga high-incidence population. Zhonghua Xiaohua Zazhi 1993;13:315-317
111  Liu XY, Zheng S, Yang G, Yu H, Zhou L, Zhang X, Shun QY, Shen GF, Shen YZ, Ding XF. Evaluaion of combined test of
       sequencial fecal occult blood and albumin in the screening of colorectal neoplasma.
       Zhongliu Fangzhi Yanjiu 1997; 24: 197-200
112  Li SY, Zhang CL, Xu ED, Yang TZ, Cheng NP, Liu YH, He YN. Evaluaion of combined test of sequencial fecal occult
       blood and albumin in the screening of colorectal neoplasma. Zhonghua Zhongliu Zazhi 1995; 17: 381-383
113  Zhou DY, Zhang YL, Feng FC, Lai ZS, Pan DS. Combined test of spa fecal occult blood and rectum mucus t-antigen in 
       the screening and follow-up of colorectal cancer. Weichangbingxue 1997;2:67-69
114  Sidransky D, Tokino T, Hamilton SR, Kinzler KW, Levin B, Frost P, Vogelstein B. Identification of ras oncogene mutations 
       in the stool of patients with curable colorectal tumors. Science 1992; 256:102-105
115  Eguchi S, Kohara N, Komuta K, Kanematsu T. Mutations of the p53 gene in the stool of patients with resectable 
       colorectal  cancer. Cancer 1996; 77(Suppl): 1707-1710
116  Sidransky D. Molecular screening: how long can we afford to wait J Natl Cancer Inst 1994; 86: 955-956
117  Luo CY, Li SY. The detection and their clinical significance of C-erbB-2 amplification and p53 mutation in the stools of 
       patients with colorectal carcinomas. Zhonghua Putong Waike Zazhi 1999; 14: 371-373
118  Lin JY, Lin H, Zhou DY, Jiang P, Zhang YL. Detection of suppress oncogene mutations in tumor tissues and stools of 
       patients with colorectal carcinoma. Zhonghua Liuxingbingxue Zazhi 1998; 19: 326
119  Yu N, Qiu HM, Ding YQ, Xu L, Zhang SJ. The relation between DNA replication error and clinicopathological features of
       colorectal carcinoma. Zhonghua Binglixue Zazhi 1998; 27: 359-361
120  Yu N, Qiu HM, Ding YQ, Xu L. MSI-a useful molecular indicator of hereditary nonpolysis colorectal cancer: a report of 4 
       cases. Diyi Junyi Daoxue Xuebao 1999;19: 160-162
121  Guo QX, Wei N, Guo CH, Lin LM, Chen BJ. Analysis on microsatellite DNA instability in sporadic nonpolyposis colorectal
       cancer. Shandong Yike Daxue Xuebao 1999; 37: 114-116
122  Wu BP, Zhang YL, Zhou DY, Gao CF, Lai ZS. Microsatellite instability, MMR gene expression and proliferation kinetics in
       colorectal cancer with famillial predisposition. World J Gastroenterol 2000;6:902-905

Reviews	Add
more>>