title: Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and 'adenoma malignum'.
abstract: Gastrointestinal phenotype in cervical adenocarcinomas was examined by immunohistochemistry and correlated with morphologic features. Antibody panels included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition, expression of p16INK4, a cyclin-dependent kinase inhibitor which is expressed in a variety of high-risk HPV-related conditions, was studied. A total of 94 invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs) and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85% whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs, indicating incomplete intestinal differentiation without a brush border in most of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates of 60% and 62%, respectively. Nuclear and cytoplasmic p16INK4 positivity was identified in 93% of UEAs, whereas 30% of MDAs were positive for p16INK4. Results in AISs were comparable to their invasive counterparts, but morphologically usual-type AISs identified in eight cases of MDA were frequently positive for HIK1083 (75%) and MUC6 (63%), and p16INK4. Of note was the existence of lobular endocervical glandular hyperplasia (LEGH) with atypical features including cytologic abnormalities, and/or papillary projection, which were identified in this study in pure form (n=3) or in association with MDAs (n=6), but not in cases of other types of adenocarcinomas. These observations indicate that gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there seems to be a possible link between MDA, and LEGH and morphologically usual-type AIS with gastric immunophenotype in histogenesis. Frequent absence of p16INK4 expression in MDAs suggests a possibility that high-risk HPV does not play a crucial role in development of MDAs, in contrast to the majority of endocervical adenocarcinomas. p16INK4 immunohistochemistry appears to be a promising diagnostic tool, but pathologists should be aware of frequent negative staining in MDAs, which can be a source of erroneous diagnosis.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medical Science, Sendai, Japan. mika@patholo2.med.tohoku.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Takako
authors.initials: T
authors.lastname: Kiyokawa
authors.forename: Sakae
authors.initials: S
authors.lastname: Hata
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Manabe
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Toru
authors.initials: T
authors.lastname: Tase
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Ikuro
authors.initials: I
authors.lastname: Sato
authors.forename: Hiroo
authors.initials: H
authors.lastname: Tateno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naganuma
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D005752:Gastric Mucins / Q000032:analysis; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008679:Metaplasia; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins / Q000032:analysis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D015260:Neprilysin / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005752:Gastric Mucins; C524625:MUC2 protein, human; C524734:MUC6 protein, human; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins; D015260:Neprilysin