Desmoglein 3 (Dsg3) expression in cancer: A tissue microarray study on 15,869 tumors

TY - JOUR

T1 - Desmoglein 3 (Dsg3) expression in cancer: A tissue microarray study on 15,869 tumors

AU - Viehweger, Florian

AU - Azem, Ahmad

AU - Gorbokon, Natalia

AU - Uhlig, Ria

AU - Lennartz, Maximilian

AU - Dwertmann Rico, Sebastian

AU - Kind, Simon

AU - Reiswich, Viktor

AU - Kluth, Martina

AU - Hube-Magg, Claudia

AU - Bernreuther, Christian

AU - Büscheck, Franziska

AU - Clauditz, Till S

AU - Fraune, Christoph

AU - Jacobsen, Frank

AU - Krech, Till

AU - Lebok, Patrick

AU - Steurer, Stefan

AU - Burandt, Eike

AU - Minner, Sarah

AU - Marx, Andreas H

AU - Simon, Ronald

AU - Sauter, Guido

AU - Menz, Anne

AU - Hinsch, Andrea

N1 - Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.

PY - 2022/12

Y1 - 2022/12

N2 - Desmoglein-3 (Dsg3) is a transmembrane glycoprotein which is preferably found in desmosomes of keratinocytes in squamous epithelium. Both loss and upregulation of Dsg3 have been implicated in cancer progression. To comprehensively evaluate Dsg3 expression in normal and neoplastic tissues, a tissue microarray containing 15,869 samples from 137 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Dsg3 immunostaining was detectable in 47 (34.3 %) tumor categories including 15 (10.9 %) tumor types with at least one strongly positive case. The highest rate of Dsg3 positivity was found in squamous cell carcinomas from various sites (71.2-97.3 %), basal cell carcinomas of the skin (41.9 %), various tumors from salivary glands (12.9-38.9 %), and in urothelial neoplasms (2.1-20.7 %). Dsg3 positivity in less than 10 % of cases was seen in 23 additional cancer categories. Dsg3 staining was almost always weak and rarely moderate in these tumors. High Dsg3 expression was linked to invasive growth in urothelial carcinoma (p < 0.0001), as well as to advanced pT stage (p = 0.0102), nodal metastasis (p = 0.0162), blood vessel infiltration (p = 0.0189) and lymph vessel infiltration (p = 0.0151) in colorectal cancer. Reduced Dsg3 expression was linked to high grade in a cohort of 599 squamous cell carcinomas from 11 different sites of origin (p < 0.0001). Associations between Dsg3 immunostaining and clinicopathological features were not found in invasive breast cancer of no special type, ductal adenocarcinomas of the pancreas and in gastric adenocarcinomas. In summary, Dsg3 expression predominates in squamous cell carcinomas and loss of Dsg3 immunostaining goes along with dedifferentiation of these tumors. The identification of focal squamous differentiation in other neoplasms may constitute a diagnostic application of Dsg3 immunohistochemistry.

AB - Desmoglein-3 (Dsg3) is a transmembrane glycoprotein which is preferably found in desmosomes of keratinocytes in squamous epithelium. Both loss and upregulation of Dsg3 have been implicated in cancer progression. To comprehensively evaluate Dsg3 expression in normal and neoplastic tissues, a tissue microarray containing 15,869 samples from 137 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Dsg3 immunostaining was detectable in 47 (34.3 %) tumor categories including 15 (10.9 %) tumor types with at least one strongly positive case. The highest rate of Dsg3 positivity was found in squamous cell carcinomas from various sites (71.2-97.3 %), basal cell carcinomas of the skin (41.9 %), various tumors from salivary glands (12.9-38.9 %), and in urothelial neoplasms (2.1-20.7 %). Dsg3 positivity in less than 10 % of cases was seen in 23 additional cancer categories. Dsg3 staining was almost always weak and rarely moderate in these tumors. High Dsg3 expression was linked to invasive growth in urothelial carcinoma (p < 0.0001), as well as to advanced pT stage (p = 0.0102), nodal metastasis (p = 0.0162), blood vessel infiltration (p = 0.0189) and lymph vessel infiltration (p = 0.0151) in colorectal cancer. Reduced Dsg3 expression was linked to high grade in a cohort of 599 squamous cell carcinomas from 11 different sites of origin (p < 0.0001). Associations between Dsg3 immunostaining and clinicopathological features were not found in invasive breast cancer of no special type, ductal adenocarcinomas of the pancreas and in gastric adenocarcinomas. In summary, Dsg3 expression predominates in squamous cell carcinomas and loss of Dsg3 immunostaining goes along with dedifferentiation of these tumors. The identification of focal squamous differentiation in other neoplasms may constitute a diagnostic application of Dsg3 immunohistochemistry.

KW - Humans

KW - Desmoglein 3/metabolism

KW - Carcinoma, Transitional Cell

KW - Urinary Bladder Neoplasms

KW - Carcinoma, Squamous Cell/pathology

KW - Adenocarcinoma

KW - Skin Neoplasms

U2 - 10.1016/j.prp.2022.154200

DO - 10.1016/j.prp.2022.154200

M3 - SCORING: Journal article

C2 - 36375372

VL - 240

JO - PATHOL RES PRACT

JF - PATHOL RES PRACT

SN - 0344-0338

M1 - 154200

ER -