Expression of laminin‐5 gamma 2 chain predicts invasion of extramammary Paget’s disease cell

Abstract

Expression of laminin-5 gamma 2 chain predicts invasion of extramammary Paget's disease cell. APMIS. 2021; 129: 3-8. Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm characterized by intraepidermal proliferation of tumor cells. The tumor cells of EMPD may sometimes invade into the dermis or metastasize into the regional lymph nodes. Several studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicating invasiveness have yet to be well characterized. Laminin-5 (Lam-5), a heterotrimer composed of three chains (a3, b3, and c2), is a major component of the basement membrane in many tissues. One of the chains, Lam-5 c2, is a marker of invasion, because it often develops as a monomer in malignant neoplasms. We investigated the expression of Lam-5 c2 and its role for the invasiveness in EMPD. Paraffin-embedded specimens of EMPD obtained from 36 patients were examined immunohistochemically for Lam-5 c2. The cases adopted into this study comprised 16 cases of intraepidermal lesions and 20 cases with dermal invasion. The basement membrane seen in normal skin disappeared in one-third of non-invasive cases and in most invasive cases. The disappearance of Lam-5 c2 in the basement membrane and its cytoplasmic expression was more observed in the invasive cases than non-invasive cases. Expression of Lam-5 c2 may be a biological marker to predict invasiveness of EMPD.

Expression of the Laminin-5γ2 Chain Is Associated With Acquisition of Malignant Traits in Ovarian Serous and Mucinous Tumors.

“…In uterine cervical adenocarcinoma, a gynecological malignancy similar to that in the present study, the cytoplasmic expression of Lam5γ2 chain was observed as the stage of the disease increased from intraepithelial carcinoma through microinvasive carcinoma to invasive carcinoma [24]. A previous report about Paget's disease showed a similar tendency between non-invasive and invasive cases, similar to the present study [25].…”

“…Lam5 is composed of three short-chain subunits, α, β, and γ that consists of α3, β3, and γ2 chains, respectively [10][11][12][13][14]. It was recognized as a ligand for urinary-type plasminogen activator receptor, uPAR, in previous studies but has recently also been used as a marker for tumor cell invasion in some human malignancies [21][22][23][24][25]. Among these three subunits, the Lam5γ2 has been reported to show aberrant expression during the development and progression of various malignant tumors [11,12,[15][16][17][18][19][20].…”

Role of ATG7-dependent non-autophagic pathway in angiogenesis

“…Laminin, a major component of the extracellular matrix, has been found to have a significant impact on vascular biological function ( Biswas et al, 2017 ; Qin et al, 2017 ). Specifically, laminin-5 is a laminin isoform consisting of α3, β3, and γ2 chains and has been reported to induce neovascularization ( He et al, 2019 ; Qian et al, 2021 ; Tohmatsu et al, 2021 ). In a study conducted by He et al, the molecular mechanism of ATG7 regulating cerebrovascular formation was investigated ( He et al, 2019 ).…”