Colorectal cancer (CRC) is a neoplastic disease in which normal mucosa undergoes a process of malignant transformation due to the progressive accumulation of molecular alterations affecting proto-oncogenes and oncosuppressor genes. Some of these modifications exert their carcinogenic potential by promoting a constitutive activation of the β-catenin signaling proliferation pathway, and when present, loss of cadherin expression also significantly contributes to the same effect. Using a combined approach of molecular and immunohistochemical analysis, we have previously demonstrated that most sporadic CRCs exhibit a down-regulated expression of a cadherin, named μ-protocadherin, that is generally observed in association with a higher proliferation rate and a worse prognosis. The aim of this report was to perform a comparative immunohistochemical assessment of μ-protocadherin and a similar cadherin, named protocadherin-24, in sporadic CRC and hereditary nonpolyposis colorectal cancer. The data obtained put in evidence that double-negative CRCs, lacking both the analyzed protocadherins, are more represented among sporadic tumors, whereas double-positive CRCs, maintaining their expression, exhibit an opposite trend. As expected, loss of protocadherin expression was accompanied by nuclear localization of β-catenin and increased positivity of the Ki-67 proliferation marker. This finding is consistent with the different clinical evolution of the 2 considered CRC sets according to which patients with hereditary nonpolyposis colorectal cancer experience a better prognosis as compared with those affected by a sporadic CRC.
|Data di pubblicazione:||2019|
|Titolo:||Loss of expression of μ-protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers|
|Autore/i:||Losi, Lorena; Lancellotti, Cesare; Parenti, Sandra; Scurani, Letizia; Zanocco-Marani, Tommaso; Buffoli, Federico; Grassia, Roberto; Ferrari, Sergio; Grande, Alexis|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.humpath.2018.09.019|
|Codice identificativo ISI:||WOS:000461725100035|
|Codice identificativo Scopus:||2-s2.0-85060214635|
|Codice identificativo Pubmed:||30296522|
|Citazione:||Loss of expression of μ-protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers / Losi, Lorena; Lancellotti, Cesare; Parenti, Sandra; Scurani, Letizia; Zanocco-Marani, Tommaso; Buffoli, Federico; Grassia, Roberto; Ferrari, Sergio; Grande, Alexis. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - 84(2019), pp. 299-308.|
|Tipologia||Articolo su rivista|
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