ENDOCRINE TUMORS OF THE CERVIX - MORPHOLOGIC ASSESSMENT, EXPRESSION OF HUMAN-PAPILLOMAVIRUS, AND EVALUATION FOR LOSS OF HETEROZYGOSITY ON 1P, 3P, 11Q, AND 17P

BACKGROUND. Cervical endocrine tumors are rare lesions, with a varied diagnostic nomenclature. A recent consensus meeting proposed a standar dized terminology. This study evaluated: 1) applicability of histopath ologic guidelines; 2) evidence of loss of heterozygosity (LOH) at sele cted sites; and 3) the presence of human papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH). METHODS. Thirty-eight cas es (patient age range, 19-88 years; mean, 48 years) were retrieved. Ou tcome data were available for 32 patients. Classification was based on architectural and cytologic features. Tissue was available from 15 ca ses for LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP 53(17p13), D1S468(1p36), and INT-2(11q13). In ten cases, tissue was an alyzed by nonisotopic ISH with HPV probes for types 6/11, 16/18, and 3 1/33. RESULTS. Tumors were divided into four groups: small cell carcin oma (SCC) (n = 25); large cell neuroendocrine carcinoma (LCNC) (n = 5) ; SCC with focal LCNC differentiation (n = 3), and carcinoid tumor (n = 5). Tumors defined as exclusively or predominantly SCC had a particu larly poor prognosis, with 20 patients dead of disease (<6 years after diagnosis) and 6 alive with disease (after <3 years of follow-up). LO H at various 3p loci (3p14, 3p21, and 3p24) was observed in eight case s. One patient demonstrated LOH on 17p(TP53). Eight of ten cases asses sed by ISH showed nuclear staining using a combined HPV-16/18 probe. C ONCLUSIONS. Cervical endocrine tumors are highly aggressive and can be subdivided into definable categories. LOH at 3p loci is a frequent fi nding, as is nuclear staining with a combined HPV-16/18 probe. LOH at 17p(TP53 locus) appears to be relatively uncommon, suggesting that p53 mutations may not be developmentally significant. Cancer 1998;83:1391 -400. (C) 1998 American Cancer Society.