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. 2020 Sep 29;12(10):2803.
doi: 10.3390/cancers12102803.

Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia

Míriam Cuatrecasas  1   2   3 , Iñigo Gorostiaga  4 , Cristina Riera  5 , Esteban Saperas  5   6 , Gemma Llort  7   8 , Irmgard Costa  9 , Xavier Matias-Guiu  2   10   11   12   13 , Cristina Carrato  14 , Matilde Navarro  13   15 , Marta Pineda  13   15 , Núria Dueñas  13   15 , Joan Brunet  13   16 , Vicente Marco  17 , Isabel Trias  18 , José Ignacio Busteros  19 , Gemma Mateu  20 , Francesc Balaguer  3   21 , María-Teresa Fernández-Figueras  6   22 , Manel Esteller  2   13   23   24 , Eva Musulén  14   22   23
Affiliations

Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia

Míriam Cuatrecasas et al. Cancers (Basel). .

Abstract

The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to MSH2 alterations. LS was confirmed in 68 patients, 53 with MSH2 mutations and 15 with EPCAM 3'-end deletions. Tissue microarrays were constructed with human normal tissues and their malignant counterparts to assist in the evaluation of EPCAM staining. Among 154 MSH2-negative lesions, 17 were EPCAM-negative, including 10 CRC and 7 colorectal polyps, and 5 of them showed only isolated negative glands. All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3'-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3'-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps.

Keywords: EPCAM; colon polyps; colorectal cancer; immunohistochemistry; lynch syndrome.

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Conflict of interest statement

F.B. received endoscopic equipment on loan from FujiFilm, consultation fees from Sysmex and Cancer Prevention Pharmaceuticals, speaker fees from Norgine, and editorial fees from Elsevier. The remainder authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
MSH2 and epithelial cell adhesion molecule (EPCAM) expressions in colorectal cancer (CRC) from EPCAM deletion carriers. (a) Loss of MSH2 expression in colorectal adenocarcinoma, mucinous type. (b) The same adenocarcinoma with a loss of EPCAM expression. Staining of normal colonic glands served as the internal positive control.
Figure 2
Figure 2
MSH2 cytoplasmic expression. (a) MSH2 cytoplasmic expression in both normal epithelial glands and in medullary colorectal cancer cells. Notice the lack of nuclear MSH2 expression in neoplastic cells. Lymphocytes in between the tumor cells showed nuclear staining and served as the internal positive control. (b) Loss of EPCAM expression in the tumor cells with normal colonic glands retaining the staining. (c) H&E staining of poorly differentiated gastric carcinoma displaying a cohesive solid pattern. (d) MSH2 staining yields a cytoplasmic expression in some of the tumor cells.
Figure 3
Figure 3
MSH2 and EPCAM expression in colorectal polyps from EPCAM deletion carriers. (a,c) Loss of MSH2 expression in colon adenomas. (b,d) Loss of EPCAM immunostaining only in isolated glands. Staining of normal colonic glands served as the internal positive control in (a,b), and (d). Lymphocytes cells were the internal positive control in (c).
Figure 4
Figure 4
H&E staining and EPCAM expression in several normal tissues. (a) Esophagus, (b) stomach, (c) small bowel, (d) colon, (e) pancreas, (f) liver, (g) parotid, (h) thyroid, (i) parathyroid, (j) endocervix, (k) endometrium, (l) teste, (m) kidney, (n) prostate, and (o) seminal vesicle.
Figure 5
Figure 5
H&E staining and EPCAM expression in several tumor tissues. (a) Squamous lung carcinoma, (b) lung adenocarcinoma, (c) neuroendocrine lung carcinoma, (d) parathyroid adenoma, (e) thyroid adenoma, and (f) papillary thyroid carcinoma.
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