Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors.

The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1 % of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCAI, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues.

Preoperative assessment of vascularity by color Doppler ultrasonography in human rectal carcinoma.

PURPOSE: Although angiogenesis assessed by immunostaining endothelial cells (microvessel density) is a well-known prognostic factor in a wide variety of human solid tumors, preoperative determination of microvessel density seems to be difficult in rectal carcinoma. Thus, we performed transanal color Doppler ultrasonography in 46 patients with rectal carcinoma to assess preoperative angiogenic status and compare it with microvessel density in surgical specimens. METHODS: Time-averaged maximal velocity, peak systolic velocity, number of vascular points, and vascular point index were conducted by color Doppler ultrasonography in 46 patients with rectal carcinoma. Number of vascular points was defined as the number of vessels with pulsation in the section of tumor. Vascular point index was defined as the average number of vascular points divided by the area assessed by color Doppler ultrasonography in the section of tumor. The profiles of number of vascular points were similar to those assessed by microangiography in five rectal carcinomas. RESULTS: Vascular point index significantly correlated with microvessel density (P < 0.0001). No significant correlation was found between microvessel density and time-averaged maximal velocity or peak systolic velocity. Vascular point index was also a better indicator of lymph node metastasis and venous invasion than microvessel density. In addition, 11 of 46 cases with postoperative hematogenous metastasis (23.9 percent) were observed prospectively. Vascular point index may be a best predictor for hematogenous metastasis from rectal carcinoma compared with peak systolic velocity, time-averaged maximal velocity, and microvessel density by receiver operating characteristic analysis. CONCLUSION: These results suggest that preoperative quantification of angiogenesis using color Doppler ultrasonography will provide quick and useful information in the management of rectal carcinoma.