Human leukocyte antigens as genetic markers in colorectal carcinoma.

PURPOSE: Similar to findings obtained for most carcinomas, the pathogenesis of colorectal cancer is considered to be multifactorial. There is strong evidence for an inherited, genetic predisposition to disease in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. There is still debate, however, about the contribution of genetic factors to the pathogenesis of sporadic colorectal cancer. The present study was undertaken to search for human leukocyte antigen associations in a group of patients with colorectal cancer and to correlate the findings with both the histology of the disease and family history. SUBJECTS AND METHODS: The allele frequencies of serologically defined human leukocyte antigen class I and II antigens were studied in 101 patients with a recent, histologically confirmed diagnosis of colorectal cancer. All individuals in this study were unrelated to each other. After surgical treatment, all patients were grouped according to the stage (Dukes Stages A, B, C, and D), differentiation (Grades 1, 2, and 3), and the site of the tumor. Patients were also classified with regard to family history for colorectal cancer. The results obtained for human leukocyte antigen frequencies were compared with those of 105 healthy control subjects (control group). RESULTS: An increased frequency of human leukocyte antigen-B18 (27.72 vs. 14.28 percent; P < 0.025; odds ratio = 2.3) and of human leukocyte antigen-DQ5 (43.56 vs. 22.5 percent; P < 0.01; odds ratio = 2.65) was observed for patients with colorectal cancer vs. control subjects, respectively. In addition, human leukocyte antigen-B18 was present with increased frequency (30.76 percent; P < 0.05; odds ratio = 2.66; and 26.67 percent; P < 0.05; odds ratio = 2.18) among patients with rectal and colon carcinoma, respectively. A higher frequency of human leukocyte antigen-DQ5 (45.33 percent; P < 0.01; odds ratio = 2.84) was observed among patients with colon carcinoma. Remarkably, human leukocyte antigen-DQ5 (50 vs. 22.5 percent; P < 0.05; odds ratio = 3.43) and human leukocyte antigen-A1 (41.66 vs. 12.38 percent; P < 0.01; odds ratio = 5.05) were found to be strongly associated with a family history of colorectal cancer. CONCLUSION: The observation of specific human leukocyte antigen associations with particular subsets of colorectal cancer strongly suggests that genetic susceptibility for the development of colorectal cancer exists. Although the multifactorial pathogenesis of colorectal cancer must be considered, human leukocyte antigens may have useful predictive and diagnostic value.

Increased estrogen receptor and epidermal growth factor receptor gene product co-expression in surgically resected gastric adenocarcinomas.

BACKGROUND: Evidence exists that estrogens influence the action of epidermal growth factor (EGF) and its receptor (EGF-R) at multiple levels. Estrogen and antiestrogen action on gastric and other gastrointestinal malignancies has been evaluated by several groups with conflicting results, and EGF-R has been implicated in the current growth factor-mediated models for gastric cancer progression. METHODS: ERs and EGF-Rs were detected immunohistochemically in a total of 53 advanced gastric carcinomas using monoclonal antibodies (mAbs) to human ERs and EGF-Rs. RESULTS: ERs were expressed in 30 (56%) and EGF-Rs in 20 (38%) of the gastric tumors. ER(+) gastric tumors were closely associated with the intestinal type (P < 0.01), whereas EGF-R(+) tumors were significantly correlated with poor differentiation status and ER(+) expression (P < 0.01). Of EGF-R(+) tumors, 85% were also ER(+). EGF-R and ER co-expression was demonstrated in 17 tumors (32% of the group). These cases were significantly corelated with poor differentiation and large tumor size upon resection (P < 0.05). CONCLUSIONS: ER and EGF-R co-expression indicates that a functional interaction between estrogens and EGF may exist in gastric cancer and that when such an interaction becomes operative, it may lead to dedifferentiation and increased tumor growth.