BCL2 and Keratin 5 Define the Uterine-Cervix-Isthmus Junction, a Transition Between Endocervical and Tubal-Like Epithelium

Abstract

A clearcut definition of the transition from the cervix to the lower uterine segment is lacking. We therefore evaluated the location of the anatomic border between the cervix and the uterine corpus. Using both morphometry and immunohistochemisty, we examined the epithelial and stromal cell types in this transition zone. In 26 patients, longitudinal sections from the cervix uteri up to the fundus uteri were paraffin embedded and immunohistochemically stained for BCL2, keratin 5, Ki-67, CD10, and CD34. Examination of the slides resulted in the identification of a junctional zone in the cranial portion of the cervix, which is characterized by a usually abrupt morphologic and immunohistochemical transition from an endocervical-type mucinous epithelium to a ciliated tubal-like epithelium and a slow transition in stromal marker expression patterns. This epithelial transition was characterized by its intense keratin 5 and BCL2 staining with accompanying Ki-67 expression in the tubal-like epithelium, whereas the endocervical epithelium was largely negative for these markers. CD10 expression was usually quite intense directly around endocervical invaginations, but the remaining stroma was negative. Toward the endometrial cavity, expression increased and endometrial stroma displayed full thickness expression for CD10. CD34 showed a reverse pattern to CD10, with moderate expression in the endocervical stroma, which disappeared in the endometrial stoma. The immunohistochemical identification of this transition may allow a more objective determination of the extension of endometrial carcinoma into the cervix in cases that are morphologically problematic. Furthermore, as ciliated tubal-like epithelium is invariably found cranial to the uterine-cervix-isthmus junction, a diagnosis of tubal metaplasia should not be made in this region and tubal-like epithelium is not indicative of a metaplastic process.

Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders

“…The KRT5 expression pattern described in the GTEx database is in agreement with previous reports of KRT 5 expression in differentiating adipose-derived stem cells [ 78 ], whole blood [ 79 ], esophagus, skin, bladder, mammary tissue [ 54 , 80 ], cervix [ 81 ], lung [ 80 , 82 ], prostate, liver, pancreas, stomach and salivary gland [ 80 , 83 ]. The finding that KRT14 expression occurs in every tissue, except for the renal medulla, is in agreement with previous reports demonstrating KRT14 expression in uterus, vagina, bladder [ 60 ] esophagus [ 54 ], mammary tissue, lung, prostate and salivary gland [ 54 , 80 ].…”

Cellular Pathology of Glandular Lesions and Uncommon Neoplasms of the Cervix

“…There are no histological landmarks which clearly delineate the junction and here there is an admixture of ciliated lower uterine segment endometrial glands and mucinous endocervical glands. It has been suggested that the uppermost mucinous gland be taken as the junction between the cervix and the lower uterine segment [ 123 ] while in another study it was suggested that the lowest ciliated gland be taken as that junction [ 124 ].…”

Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix

“…[6][7][8][9] Squamous metaplasia is the result of proliferation and maturation of a unique subset of progenitor cells, the socalled reserve cells, which are sporadically seen under endocervical columnar cells up to the second junction at the beginning of the endometrium. 1,7,10 Upon differentiation, reserve cells acquire squamous characteristics, initially forming immature squamous metaplastic epithelium, subsequently maturating into a squamous epithelium that is indistinguishable from the original ectocervical squamous epithelium. 6 There is a general consensus that reserve cells can be regarded as a progenitor cell population, capable of generating squamous type epithelium.…”