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

• Published in: Modern pathology Vol. 17; no. 8; pp. 962 - 972
• Main Authors: Mikami, Yoshiki, Kiyokawa, Takako, Hata, Sakae, Fujiwara, Keiichi, Moriya, Takuya, Sasano, Hironobu, Manabe, Toshiaki, Akahira, Jun-Ichi, Ito, Kiyoshi, Tase, Toru, Yaegashi, Nobuo, Sato, Ikuro, Tateno, Hiroo, Naganuma, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2004; Elsevier Limited
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenoma - metabolism; Adenoma - pathology; adenoma malignum; Chromogranin A; Chromogranins - analysis; Cyclin-Dependent Kinase Inhibitor p16 - analysis; endocervical adenocarcinomas; Female; Gastric Mucins - analysis; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - pathology; gastrointestinal phenotype; HIK1083; Humans; Hyperplasia; Immunohistochemistry; LEGH; Metaplasia; MUC; Mucin-2; Mucin-6; Mucins - analysis; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Neprilysin - analysis; p16INK4; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; endocervical adenocarcinomas; p16INK4; adenoma malignum; LEGH; MUC; HIK1083; gastrointestinal phenotype
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800148

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.