外阴鳞状细胞癌：倍体、人乳头瘤病毒、p53和视网膜母细胞瘤蛋白的研究

Squamous cell carcinoma of the vulva: study of ploidy, HPV, p53, and pRb.

作者信息

Lerma E, Matias-Guiu X, Lee S J, Prat J

机构信息

Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Spain.

出版信息

Int J Gynecol Pathol. 1999 Jul;18(3):191-7. doi: 10.1097/00004347-199907000-00001.

DOI:10.1097/00004347-199907000-00001

PMID:12090585

Abstract

Seventy-one cases of invasive squamous cell carcinoma (ISCC) of the vulva were compared with 18 cases of vulvar intraepithelial neoplasia (VIN) and 21 cases of lichen sclerosus. Ploidy was studied by image analysis, HPV-DNA by PCR, and p53 and pRb by immunohistochemistry. Univariate and multivariate statistical analyses were performed. The mean age of the patients with ISCC was 70.6 years; only 8.5% were < 60 (range, 43-89) years. For the 43 patients with follow-up, FIGO surgical stages were I in 16.2%, II in 48.8%, III in 27.9%, and IV in 6.9%. The 5-year survival was 90% for the patients with curative surgery (vulvectomy and lymphadenectomy) and 32% for those with tumors in stages III to IV. Previous history of nonneoplastic epithelial alterations was recorded in 54%. Vascular invasion was detected in 4.3% and perineural invasion in 21.4%. Inguinal lymph node metastases were present in 34.9% of the cases. Fifty-one (72%) ISCCs were aneuploid, HPV-DNA-16 was detected in 7 (12.3%) cases, overexpression of p53 was found in 40 (56%), and pRb expression was negative in 15 (21.4%). Fifteen cases (80%) of VIN were aneuploid, 5 (27.7%) contained HPV-DNA, 11 (61%) were positive for p53, and all immunoreacted for pRb. All lichen sclerosus cases were diploid, did not contain HPV-DNA, failed to stain for p53, and were positive for pRb. Our study confirmed the prognostic value of conventional pathological features: stage, lymph node metastasis, histological grade, and vascular and perineural invasion; all were statistically significant for survival in the univariate analysis. Also, ploidy was significant in patients with stages I and II tumors. The only significant variable in the multivariate analysis was stage. p53 overexpression appears as a late event in vulvar carcinogenesis, but it may occur before tumor invasion. Lack of pRb expression can occur in vulvar neoplasia, but it does not seem to play any role in the initiation or prognosis of vulvar ISCC.

摘要

将71例外阴浸润性鳞状细胞癌（ISCC）与18例外阴上皮内瘤变（VIN）及21例硬化性苔藓进行比较。通过图像分析研究倍体，采用聚合酶链反应（PCR）检测人乳头瘤病毒（HPV）-DNA，应用免疫组织化学检测p53和视网膜母细胞瘤蛋白（pRb）。进行单因素和多因素统计分析。ISCC患者的平均年龄为70.6岁；年龄小于60岁者仅占8.5%（范围43 - 89岁）。43例有随访资料的患者中，国际妇产科联盟（FIGO）手术分期为I期者占16.2%，II期者占48.8%，III期者占27.9%，IV期者占6.9%。接受根治性手术（外阴切除加淋巴结清扫）患者的5年生存率为90%，而III - IV期肿瘤患者的5年生存率为32%。54%的患者有非肿瘤性上皮改变病史。4.3%检测到血管侵犯，21.4%检测到神经侵犯。34.9%的病例存在腹股沟淋巴结转移。51例（72%）ISCC为非整倍体，7例（12.3%）检测到HPV-DNA-16，40例（56%）发现p53过表达，15例（21.4%）pRb表达阴性。15例VIN（80%）为非整倍体，5例（27.7%）含有HPV-DNA，11例（61%）p53阳性，所有病例pRb免疫反应均为阳性。所有硬化性苔藓病例均为二倍体，不含HPV-DNA，p53染色阴性，pRb阳性。我们的研究证实了传统病理特征的预后价值：分期、淋巴结转移、组织学分级以及血管和神经侵犯；在单因素分析中，所有这些因素对生存均有统计学意义。此外，倍体对I期和II期肿瘤患者也有意义。多因素分析中唯一有意义的变量是分期。p53过表达在外阴癌发生过程中似乎是一个晚期事件，但可能在肿瘤侵犯之前就已发生。外阴肿瘤可出现pRb表达缺失，但它似乎在外阴ISCC的发生或预后中不起任何作用。