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 standardized terminology. This study evaluated: 1) applicability of histopathologic guidelines; 2) evidence of loss of heterozygosity (LOH) at selected sites; and 3) the presence of human papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH).


METHODS
Thirty-eight cases (patient age range, 19-88 years; mean, 48 years) were retrieved. Outcome data were available for 32 patients. Classification was based on architectural and cytologic features. Tissue was available from 15 cases for LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP53(17p13), D1S468(1p36), and INT-2(11q13). In ten cases, tissue was analyzed by nonisotopic ISH with HPV probes for types 6/11, 16/18, and 31/33.


RESULTS
Tumors were divided into four groups: small cell carcinoma (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 particularly poor prognosis, with 20 patients dead of disease (<6 years after diagnosis) and 6 alive with disease (after <3 years of follow-up). LOH at various 3p loci (3p14, 3p21, and 3p24) was observed in eight cases. One patient demonstrated LOH on 17p(TP53). Eight of ten cases assessed by ISH showed nuclear staining using a combined HPV-16/18 probe.


CONCLUSIONS
Cervical endocrine tumors are highly aggressive and can be subdivided into definable categories. LOH at 3p loci is a frequent finding, 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.
Department and Laboratory of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
C
C
Mannion
W S
WS
Park
Y G
YG
Man
Z
Z
Zhuang
J
J
Albores-Saavedra
F A
FA
Tavassoli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D019656:Loss of Heterozygosity; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology