Prognostic value of immunohistochemistry in gastric neuroendocrine (carcinoid) tumors.
Three subtypes of enterochromaffin-like cell tumors (carcinoids) have been described: type I, associated with chronic atrophic gastritis; type II, multiple endocrine neoplasia 1 and Zollinger-Ellison syndrome; and type III, sporadic tumors.


OBJECTIVE
(i) To investigate the immunoexpression of Ki-67, p53 and Bcl-2 proteins in enterochromaffin-like cell (carcinoid) tumors and (ii) to evaluate the prognostic value of these markers.


METHODS
Fifty-four samples from 21 patients with gastric carcinoid tumors were sectioned and immunostained using avidin-biotin peroxidase method.


RESULTS
The mean age was 62.2+/-11.4 years (36-83 years-old) and 13 (61.9%) were women. Type I lesions were detected in 61.9% and type III in 38.1%. Tumors were single in 10 (47.6%) and were multiple and/or multicentric in 11 (52.4%). Nuclear p53 immunoreactivity was observed in 6/21 patients (28.6%), and all of them were type III tumors (6/8), compared with no p53 expression in type I (0/13), P=0.0002. p53 expression was also associated with high degree of cell proliferation (Ki-67-positive nuclear cells), P=0.00001. Bcl-2 expression was either unreactive or weakly positive in all tumor lesions. The mean follow-up period was 50.4 months (SD=45.2), varying from 6 to 144 months. Overall survival time of patients with positive p53 expression and high proliferative rate was significantly lower than that of negative patients (14.4 vs 123 months, P=0.0007).


CONCLUSIONS
(i) p53 immunoexpression associated with high proliferative rate was useful to distinguish between type I and type III gastric carcinoid tumors and (ii) these markers were able to predict a shorter survival.
Safatle-Ribeiro
Adriana V
AV
Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil. adrisafatleribeiro@terra.com.br
Ribeiro
Ulysses
U
Corbett
Carlos E P
CE
Iriya
Kiyoshi
K
Kobata
Cristina H P
CH
Sakai
Paulo
P
Yagi
Osmar K
OK
Pinto
Paulo E
PE
Zilberstein
Bruno
B
Gama-Rodrigues
Joaquim
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005773:Gastroscopy; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53