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'

Yoshiki Mikami, Takako Kiyokawa, Sakae Hata, Keiichi Fujiwara, Takuya Moriya, Hironobu Sasano, Toshiaki Manabe, Jun Ichi Akahira, Kiyoshi Ito, Toru Tase, Nobuo Yaegashi, Ikuro Sato, Hiroo Tateno, Hiroshi Naganuma

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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 p16 INK4 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.

Original languageEnglish
Pages (from-to)962-972
Number of pages11
JournalModern Pathology
Volume17
Issue number8
DOIs
Publication statusPublished - 2004 Aug

Keywords

  • Adenoma malignum
  • Endocervical adenocarcinomas
  • Gastrointestinal phenotype
  • HIK1083
  • LEGH
  • MUC
  • P16

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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