Keratin profiles in normal/hyperplastic prostates and prostate carcinoma

Abstract

Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34 beta E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35 beta H11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/hyperplastic prostates, RPN1162, 35 beta H11, CK5 and M20 stained luminal cells without staining basal cells, and 34 beta E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35 beta H11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34 beta E12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.

Basal epithelial stem cells are efficient targets for prostate cancer initiation

“…Prostate stem cells are thought to reside in the basal cell layer of the ducts, and in the mouse they predominate in the region of the gland that is proximal to the urethra (6,7). Clinical observations that the majority of human prostate cancer cells express luminal cell markers have led many to propose that these cells are the source of prostate cancer initiation (8). The neoplasms that develop in the Rb −/− p53 −/− knockout mouse model express the stem cell marker Sca-1 and arise in the proximal region of the gland (9).…”

Cancer stem cell markers in common cancers – therapeutic implications

“…There is more than one stem/ progenitor cell population present in prostate cancer. The majority of human prostate adenocarcinoma cells express the luminal epithelial cell markers CK8/18, PSA and PAP [87] but lack basal cell markers. A small cancer cell fraction in primary prostate carcinoma tissues and the majority of prostate cancer metastases express the basal cell markers CK5/14, CD44 and p63 (Table 2) [25].…”

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

“…NE cells are rare (Ͻ1% of the total), have distinctive projections that allow them to contact epithelial neighbors located several cell diameters away, and secrete a variety of neuropeptides and neurotransmitters (14)(15)(16)(17). Conventional adenocarcinoma of the prostate (CaP) is the most commonly diagnosed cancer and the second leading cause of cancer death in males (18): it displays features common to luminal͞secretory cells (19)(20)(21)(22)(23). Pure NE cell tumors of the prostate are rare but aggressive (2).…”