title: Cervical Carcinomas With Neuroendocrine Differentiation: A Report of 28 Cases With Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin With Coexisting Squamous and Adenocarcinomas.
abstract: Cervical neuroendocrine carcinomas are rare, aggressive tumors and their immunohistochemical features and clonal relationship to coexisting tumors are incompletely described. Twenty-eight cases were identified (17 small cell, 9 large cell, and 2 mixed), 10 of which had an invasive squamous or adenocarcinoma component. Staining for synaptophysin, chromogranin A, TTF1, c-kit, CD44, and p16 was performed. Analyses for loss of heterozygosity (LOH) at 5 polymorphic microsatellite markers (D3S1300, D9S171, D11S914, D13S319, and TP53) and X-chromosome inactivation were performed. Of 17 cases with available blocks, 13 (76%) were synaptophysin+, 8 (47%) were chromogranin A+, 8 (47%) were TTF1+, 7 (41%) were c-kit+, and 6 (35%) were CD44+. Strong patchy or strong diffuse p16 staining was seen in all cases. LOH and X-chromosome inactivation analysis were performed for 17 cases, 8 of which had a coexisting squamous or adenocarcinoma component. Five of the 8 (63%) cases with 2 components showed allelic loss in both components. All 5 of these cases demonstrated identical LOH between the neuroendocrine and squamous or adenocarcinoma components. Nonrandom X-chromosome inactivation was seen in the neuroendocrine and other components in 4 of the 8 cases. In all 4 cases the pattern of inactivation was identical between the 2 components. Cervical neuroendocrine carcinomas have features similar to other extrapulmonary neuroendocrine carcinomas, including expression of TTF1, c-kit, and CD44. Consistent staining for p16 is also seen. Concordant genetic alterations support common clonal origin for neuroendocrine carcinomas with a coexisting squamous or adenocarcinoma component.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Emerson
authors.forename: Helen
authors.initials: H
authors.lastname: Michael
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Roth
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049951:X Chromosome Inactivation
chemical_list: D014408:Biomarkers, Tumor