Alterations in the p16INK4a/cyclin D1/RB pathway in gastrointestinal tract endocrine tumors.
A series of 76 cases of gastrointestinal tract endocrine tumors, including 21 poorly differentiated endocrine carcinomas (PDECs, small cell carcinomas) and 55 well-differentiated endocrine neoplasms (WDENs, carcinoids), 18 metastatic and 37 nonmetastatic rectal carcinoids, were examined by immunohistochemical analysis for p16INK4a, cyclin D1, and retinoblastoma protein (pRB) expression. Overexpression of p16INK4a was noted in 16 (76%) of the PDECs and none of the WDENs (P < .0001). Loss of pRB expression was demonstrated in 14 (67%) of the PDECs and 17 (31%) of the WDENs (P = .004). Overexpression of cyclin D1 was noted in 49 (89%) of the WDENs and 3 (14%) of the PDECs (P < .0001). Loss of pRB expression was noted in 11 (61%) of 18 metastatic WDENs and only 6 (16%) of 37 nonmetastatic WDENs (P = .001). The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors, and the loss of expression of pRB may be helpful in identifying patients at high risk of metastasis in rectal WDENs.
Li
Anna Fen-Yau
AF
Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
Li
Alice Chia-Heng
AC
Tsay
Shyh-How
SH
Li
Wing-Yin
WY
Liang
Wen-Yih
WY
Chen
Jeou-Yuan
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000096:biosynthesis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1