Furihata M, Yamasaki I, Ohtsuki Y, Sonobe H, Morioka M, Yamamoto A, Terao N, Kuwahara M, Fujisaki N
Department of Pathology II, Kochi Medical School, Japan.
Int J Cancer. 1995 Oct 20;64(5):298-303. doi: 10.1002/ijc.2910640503.
Ninety-eight cases of transitional-cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type-16 and type-18 DNA by in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fresh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by polymerase chain reaction (PCR). Thirty-two tumors were positive for HPV DNAs, including 6 double-positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivity. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 point mutation was detected in 7 of 26 cases, 6 of which were also positive for p53. HPV type-16 DNA was detected in 6 cases by PCR, 4 of which were also ISH-positive. Overexpressed p53 was frequently detected in invasive and non-papillary tumors (p < 0.01) and in high-grade tumors (p < 0.05). HPV infection was more common in non-invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overexpression (mutation) of p53 may be an early event and be related to phenotypes of tumor-cell growth patterns and progression.
对98例肾盂和输尿管移行细胞癌（TCC）病例（包括发育异常病变）进行了研究，通过针对每种人乳头瘤病毒（HPV）病毒类型的DNA探针原位杂交（ISH）检测HPV-16型和18型DNA在肿瘤中的掺入情况。还进行了p53表达的免疫组织化学分析。对26例患者的新鲜肿瘤组织进行了外显子4至9的p53突变直接测序研究以及聚合酶链反应（PCR）HPV感染检测。32例肿瘤HPV DNA呈阳性，包括6例双阳性病例。在这些肿瘤中，21例（66%）的相邻发育异常病变也显示出相同的反应性。26例检测到p53过表达。在这26例中的19例（73%）发育异常病变中也检测到p53表达。3例HPV DNA和p53抗体均呈阳性。26例中有7例检测到p53点突变，其中6例p53也呈阳性。通过PCR在6例中检测到HPV-16型DNA，其中4例ISH也呈阳性。侵袭性和非乳头状肿瘤（p<0.01）以及高级别肿瘤（p<0.05）中经常检测到p53过表达。HPV感染在非侵袭性和乳头状肿瘤中更为常见（p<0.05）。这些发现表明，HPV感染或p53的过表达（突变）可能是早期事件，并且与肿瘤细胞生长模式和进展的表型有关。
