Stoler M H, Mills S E, Gersell D J, Walker A N
University of Rochester, New York.
Am J Surg Pathol. 1991 Jan;15(1):28-32. doi: 10.1097/00000478-199101000-00003.
Small-cell undifferentiated carcinomas comprise a rare but aggressive subset of uterine cervical neoplasms. Analogous to small-cell anaplastic carcinoma of the lung, these tumors frequently exhibit neuroendocrine differentiation. Although human papillomaviruses (HPV) types 16 and 18 are strongly associated with the development of cervical squamous carcinoma, there is as yet little information describing the relationship of these viruses to small-cell carcinomas. To address this question, we analyzed 20 cases of small-cell carcinoma of the cervix using in situ hybridization to detect HPV gene expression. In addition, immunohistochemistry was used to evaluate three markers of neuroendocrine differentiation. Eighteen of 20 tumors (90%) demonstrated some evidence of neuroendocrine differentiation; 17 of 20 (85%) expressed HPV type 16 or 18 messenger RNA. Of the neuroendocrine-positive cases, 14 of 18 expressed HPV 18 messenger RNA. In contrast, both of the cases with squamous differentiation were HPV 16 positive. These findings broaden the spectrum of HPV-associated cervical neoplasia and strongly suggest that HPV 18 is a viral type specifically associated with cervical small-cell neuroendocrine carcinomas.
小细胞未分化癌是子宫颈肿瘤中一种罕见但侵袭性强的亚型。与肺小细胞间变性癌类似，这些肿瘤常表现出神经内分泌分化。虽然16型和18型人乳头瘤病毒（HPV）与宫颈鳞状癌的发生密切相关，但关于这些病毒与小细胞癌之间关系的描述尚少。为解决这个问题，我们采用原位杂交检测HPV基因表达，对20例宫颈小细胞癌进行了分析。此外，还运用免疫组化评估神经内分泌分化的三种标志物。20例肿瘤中有18例（90%）显示出神经内分泌分化的某些证据；20例中有17例（85%）表达16型或18型HPV信使核糖核酸。在神经内分泌阳性病例中，18例中有14例表达18型HPV信使核糖核酸。相比之下，2例鳞状分化病例均为16型HPV阳性。这些发现拓宽了HPV相关宫颈肿瘤的范围，并有力地表明18型HPV是一种与宫颈小细胞神经内分泌癌特异性相关的病毒类型。
