Angiogenesis of AFP producing gastric carcinoma: correlation with frequent liver metastasis and its inhibition by anti-AFP antibody.

We studied roles of angiogenesis in patients with alpha-fetoprotein (AFP)-producing gastric carcinoma (APGC), which is well known to have a poor prognosis and frequent liver metastases. Immunohistochemical analyses were conducted using antibodies against alpha-fetoprotein, factor VIII (endothelial cells) and vascular endothelial growth factor (VEGF). Archival specimens of APGC (n=25) and non-APGC (n=68) were studied. Expressions of vessel density and VEGF were significantly higher in APGC than those in non-APGC (p<0.001). There is a correlation among the AFP expression, the vessel density and the VEGF expression in APGC (p<0.001). Next, we studied the effects of anti-AFP antibody on APGC xenotransplanted in nude mice. There is significant inhibition of tumor growth in the treatment groups compared to the control groups in 2 APGC lines (p<0.01). There were also significant differences in serum AFP and VEGF levels between treatment groups and non-treatment groups in 2 APGC lines, but not in a non-APGC line. Moreover, vessel densities of the treatment groups were significantly lower than those of the control groups in the two lines. These findings thus suggest that the biological behavior of APGC is angiogenesis-dependent. Down-regulation of angiogenesis by anti-AFP antibody suggest that AFP itself may up-regulate angiogenesis, and the treatment by antibody could have anti-angiogenic effects, inhibiting metastasis, especially liver metastasis in APGC.

Non-Hodgkin's lymphoma in a patient with probable hereditary nonpolyposis colon cancer: report of a case and review of the literature.

PURPOSE: Hereditary nonpolyposis colorectal cancer kindreds are frequently associated with cancers in various organs, including endometrium, stomach, and ovary. However, hematologic malignancy has rarely been reported in association with this cancer syndrome. We present here the case of a probable hereditary nonpolyposis colon cancer patient in whom non-Hodgkin's lymphoma developed after curative resection of colon cancer. Our experience with this rare case encouraged us to review the literature for reports indicating a possible relationship between these diseases. RESULTS: A 52-year-old male whose family history was consistent with the criteria for hereditary nonpolyposis colon cancer underwent right hemicolectomy for ascending colon cancer. Histologically the tumor consisted of adenocarcinoma that was moderately differentiated with mucinous foci and that invaded beyond the muscularis propria. Neither metastasis nor lymphoma was found in paracolonic lymph nodes. Eight months after surgery, the patient developed non-Hodgkin's lymphoma of T-cell origin involving the ileum and lungs. Both colon cancer and lymphoma frequently showed microsatellite DNA instability, sharing alteration in a locus of chromosome 7 (D7S501). CONCLUSION: A possible association of hematologic malignancy with hereditary nonpolyposis colon cancer reported in the literature, together with a report that MSH2-deficient mice are susceptible to malignant lymphoma, strongly supports the finding that this patient's lymphoma was related to hereditary nonpolyposis colon cancer. Overall, this case manifested a distinct clinical course similar to that observed in an animal model that is deficient in DNA mismatch repair machinery, thus providing scientific and clinical implications for understanding the molecular basis of these tumors and for critical management of hereditary nonpolyposis colorectal cancer patients, respectively.