Abstracts
1999 Digestive Disease Week

# 2142 EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA RECEPTOR II AND INSULIN-LIKE GROWTH FACTOR 1-RECEPTOR IN HUMAN DUCTAL CARCINOMA OF THE PANCREAS.
R C Karl, L Lu, S Teng, D Coppola, R C Karl, Univ of South Florida, Tampa, FL

Three types of transforming growth factor receptors (TGF-bR's) have been identified in pancreatic ductal cancer (PDA). The activation of TGF-b RII is believed to inhibit cellular growth. It has been suggested that reduced TGF-b RII expression may potentiate the tumorigenic effect of the insulin-like growth factor 1 receptor (IGF1-R) in PDA. Methods: To study variations in the expression of TGF-b RII and IGF1-R in human PDA, formalin-fixed paraffin-imbedded tissue sections of 47 cases of PDA were immunostained for both receptors using the avidin-biotin-peroxidase (ABC) method. We used an IGF1-R rabbit polyclonal antibody (Santa Cruz, B.I., Santa Cruz, Ca; dilution: 1:100) toward the b subunit of the human IGF1-R, and a rabbit polyclonal antibody recognizing a carboxy terminal domain of the pre-human TGF-b RII (Santa Cruz B.I., Santa Cruz, CA; dilution 1:100). Positive stainings were quantified by semiquantitative criteria, considering the percentage of stained areas and intensity of staining. Results: TGF-b RII was absent in 17% of cases. Moderate to strong TGF-b RII cytoplasmic staining was predominantly detected in low grade PDA. All the tumors revealed strong submembranous IGF1-R stain. Conclusions: The strong expression of IGF1-R in the majority of PDA supports the role of this cell receptor in human pancreatic carcinogenesis. The loss of the inhibitory effect of TGF-b RII in poorly differentiated PDA may potentiate the IGF1-R autocrine loop, resulting in a less differentiated phenotype.

Grade No.of Cases TGF-b(%)				RII Positive Cases IGF1-R Positive Cases (%)
		Weak	Moderate	Strong	Weak	Moderate	Strong
1	11	2(18)	4(36.5)	5(45)	1(9)	2(18)	8(74)
2	22	10(45)	5(23)	4(18)	2(9)	4(18)	16(73)
3	14	7(50)	1(4)	1(4)	1(7)	2(14)	11(79)
Total	47	19(40)	10(21)	10(21)	4(9)	8(17)	35(74)
* 8 cases were TGF-b RII negative

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