hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: A systematic review

Table 3 hENT1 expression levels, cut-offs and grouping

Ref.	Method	Grading	Reference cells	Groups (n)
Spratlin et al[9]	IHC	0-2 based on relative intensities of staining.	Langerhans cells, lymphocytes.	Dichotomized:
		0 = absence of staining		Low = 0 (12)
		1 = intermediate staining		High = 1 and 2 (9)
		2 = most intense staining
Giovannetti et al[10]	RT-PCR	Gene-expression ratio with GAPDH, expressed as tertiles		Gene expression tertiles:
		GAPDH/target gene ratio		Low < 1.06 (27)
				Intermediate 1.06-1.38 (28)
				High ≥ 1.38 (26)
				Dichotomized:
				By medians
				Low < 1.23 (44)
				High ≥ 1.23 (37)
Farrell et al[12]	IHC	Based on relative intensities.	Lymphocytes	Dichotomized:
		High = strong reactivity in > 50% of neoplastic cells.		No (18)1
		No = no staining in > 50%		vs
		Low = all cases between High and No.		Low/high (73)1
Maréchal et al[3]	IHC	0-3 based on staining intensities	Langerhans cells	Dichotomized:
		0 = no staining	Lymphocytes	Low < 80 (26)
		1 = weakly positive		(final score)
		2 = moderately positive
		3 = strongly positive		High = ≥ 80 (19)
		Final score calculated: multiplying intensity score and the percentage of the specimen. Weighted score 0-300
Fujita et al[8]	RT-PCR	Level of mRNA calculated from standard curve constructed with total RNA from Capan-1, a human pancreatic cancer cell line		mRNA split into high/low groups using recursive descent partitioning. Cut-off 0.5
				Low (26)1
				High (14)
Maréchal et al[1]	IHC	0-2 based on staining intensities	Lymphocytes	Dichotomized:
		Quantified as Farrell		Low/moderate (136)1
				High (86)1
Kawada et al[2]	IHC	0-2 based on staining intensities.	Langerhans cells	Negative = 0-1 (41)
		1 = same intensity as control.		Positive = 2 (22)
Morinaga et al[21]	IHC	Staining intensity and percentage of positive tumor cells scored and given a hENT1-score by calculating the two		Low = hENT1 score 0-3 (11)
		Staining 0-3 where		High = hENT1 score 4-6 (16)
		0 = no
		1= weakly pos
		2 = moderately pos
		3 = strongly pos
		Percentage:
		0 = no positive
		1 ≤ 50% positive cells
		2 = 50%-80% positive cells
		3 = ≥ 80%
Murata et al[22]	IHC	Staining intensity + extent of positive staining	Langerhans cells	Dichotomized:
		Intensity:		Negative = low and intermediate (16)
		0 = no staining
		1 = weakly positive		Positive = high (39)
		2 = moderately positive
		3 = strongly positive
		Extent staining:
		High = score 3 > 50% cells
		Low = score 0 or 1 > 50%
		Intermediate = all others
Nakagawa et al[23]	IHC	Staining intensities:	Langerhans cells	Low = grade 0 or 1 in > 50% (31)
		0 = not stained		High = grade 2 or 3 in > 50% of cells (78)
		1 = faintly stained
		2 = weakly stained
		3 = as strongly as islet cells

¹In gem arm. GAPDH: Glyceraldehyde 3-phosphate dehydrogenase.