Loss of the adhesion molecule CEACAM1 is associated with early biochemical recurrence in TMPRSS2:ERG fusion‐positive prostate cancers

Abstract

Altered expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity. Immunostaining was interpretable in 13,625 cancers and was considered high in 28%, low in 43% and absent in 29% of tumors. Low and lost CEACAM1 expression was strongly linked to adverse tumor features including high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, a high number of genomic deletions and early biochemical recurrence (p < 0.0001 each). Subset analysis of molecularly defined cancer subsets revealed that these associations were strongest in V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-positive cancers and that CEACAM1 loss was prognostic even in tumors harboring genomic deletions of the phosphatase and tensin homolog tumor suppressor (p < 0.0001). Multivariate analysis suggested that CEACAM1 analysis can provide independent prognostic information beyond established prognosis parameters at the stage of the initial biopsy when therapy decisions must be taken. In conclusion, loss of CEACAM1 expression predicts poor prognosis in prostate cancer and might provide clinically useful prognostic information particularly in cancers harboring the TMPRSS2:ERG fusion.A.M.L. and W.R. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

Identification of calmodulin‐like protein 5 as tumor‐suppressor gene silenced during early stage of carcinogenesis in squamous cell carcinoma of uterine cervix

“…Alternations of cell adhesion molecules are, on the other hand, involved in the steps of carcinogenesis. [10][11][12][13] Being a kind of tumor suppressor gene, cell-to-cell adhesion is usually reduced or lost during the process of carcinogenesis, 10,11,13,14 which promotes tumor progression and is a prerequisite to carcinoma invasion and metastasis. 13 In our study, with the aim of finding a novel molecular mechanism that forms a spinous structure that is related to extremely strong cell-tocell adhesion in the stratified squamous epithelium, we first produced a broad panel of monoclonal antibodies (MAbs) by immunizing mouse crude squamous tissue samples, then selected through morphological screening a MAb, 11B3, that recognizes the spinous structure.…”

“…While this spinous structure is thought to derive from the shrinkage of microfilaments between desmosomes, since desmosome‐microfilament structures are rather universally distributed among all kinds of epithelial cells, it is not clear why this particular spinous structure is formed almost exclusively among stratified squamous epithelia. Alternations of cell adhesion molecules are, on the other hand, involved in the steps of carcinogenesis 10‐13 . Being a kind of tumor suppressor gene, cell‐to‐cell adhesion is usually reduced or lost during the process of carcinogenesis, 10,11,13,14 which promotes tumor progression and is a prerequisite to carcinoma invasion and metastasis 13 …”

“…Alternations of cell adhesion molecules are, on the other hand, involved in the steps of carcinogenesis 10‐13 . Being a kind of tumor suppressor gene, cell‐to‐cell adhesion is usually reduced or lost during the process of carcinogenesis, 10,11,13,14 which promotes tumor progression and is a prerequisite to carcinoma invasion and metastasis 13 …”

CEACAM1 Is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma

“…For instance, CEACAM1 may play an anticancer role in breast cancer and prostate cancer, and animal experiments have also demonstrated that breast cancer cells or prostate cancer cells overexpressing CEACAM1 have a reduced tumorigenic capacity [ 23 – 25 ]. In addition, CEACAM1 expression was significantly reduced in breast and prostate cancers and predicts a poor prognosis for these cancers [ 26 , 27 ]. In the present study, we investigated the expression of CEACAM1 in the development and progression of ccRCC and its prognosis.…”

Value of three-dimensional visualization of preoperative prostatic magnetic resonance imaging based on measurements of anatomical structures in predicting positive surgical margin after radical prostatectomy

“…Meanwhile, moderate or strong heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) immunostaining was relevant to positive surgical margin and adverse tumor features ( 21 ). Nevertheless, low or negative expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) have linked to PSM in patients with ERG fusion-positive PCa ( 22 ). In addition to the abnormal expression of genes or proteins which included BRCA1-associated protein-1 (BAP1), RNA-binding motif protein 3 (RBP) and Fas-associated death domain-containing protein phosphorylation (FADD) by immunohistochemical analysis, changes of mutational level are also strongly associated with PSM by fluorescence in situ hybridization analysis ( 2 , 23 – 25 ).…”