Synaptophysin expression in V600EBRAF-mutated advanced colorectal cancers identifies a new subgroup of tumours with worse prognosis

被引：10

作者：

Fassan, Matteo ^{[1
]}

Milione, Massimo ^{[2
]}

Maddalena, Giulia ^{[3
]}

Cremolini, Chiara ^{[4
]}

Schirripa, Marta ^{[3
]}

Pietrantonio, Filippo ^{[5
,6
]}

Pella, Nicoletta ^{[7
]}

Dell'Aquila, Emanuela ^{[8
]}

Sperti, Elisa ^{[9
]}

Zichi, Clizia ^{[9
]}

Bergamo, Francesca ^{[3
]}

Volante, Marco ^{[10
]}

Boccaccino, Alessandra ^{[4
]}

Morano, Federica ^{[5
]}

Cortiula, Francesco ^{[7
,11
]}

De Maglio, Giovanna ^{[12
]}

Rimassa, Lorenza ^{[13
,16
]}

Smiroldo, Valeria ^{[13
]}

Calvetti, Lorenzo ^{[14
]}

Aprile, Giuseppe ^{[14
]}

Salvatore, Lisa ^{[15
]}

Santini, Daniele ^{[8
]}

Salmaso, Roberta ^{[1
]}

Centonze, Giovanni ^{[2
]}

Biason, Paola ^{[3
]}

Borga, Chiara ^{[1
]}

Lonardi, Sara ^{[3
]}

Zagonel, Vittorina ^{[3
]}

Dei Tos, Angelo P. ^{[1
]}

Di Maio, Massimo ^{[9
]}

Loupakis, Fotios ^{[3
]}

机构：

[1] Univ Padua, Dept Med DIMED, Surg Pathol Unit, Padua, Italy

[2] Fdn IRCCS Ist Nazl Tumori, Dept Pathol & Lab Med, Pathol Div 1, Milan, Italy

[3] Veneto Inst Oncol IOV IRCCS, Dept Oncol, Unit Oncol 1, Padua, Italy

[4] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy

[5] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[6] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy

[7] Univ & Gen Hosp, Dept Oncol, Udine, Italy

[8] Campus Biomed Univ Rome, Dept Med Oncol, Rome, Italy

[9] Univ Turin Umberto I Ordine Mauriziano Hosp, Dept Oncol, Turin, Italy

[10] Univ Turin, Dept Oncol, San Luigi Hosp, Orbassano, TO, Italy

[11] Univ Udine, Dept Med DAME, Udine, Italy

[12] Univ Hosp Udine, Dept Pathol, Udine, Italy

[13] IRCCS Humanitas Res Hosp, Humanitas Canc Ctr, Med Oncol & Hematol Unit, Milan, Italy

[14] San Bortolo Gen Hosp, Dept Oncol, AULSS8 Ber, Vicenza, Italy

[15] Fdn Policlin Univ Agostino Gemelli IRCCS, UOC Oncol, Rome, Italy

[16] Humanitas Univ, Dept Biomed Sci, Milan, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 146卷

关键词：

Colorectal cancer; Synaptophysin; (V600E)BRAF; Immunohistochemistry; Neuroendocrine; Prognostic markers; NEUROENDOCRINE DIFFERENTIATION; BRAF MUTATIONS; CARCINOMA; ADENOCARCINOMAS; PHENOTYPE; SUBTYPES; CELLS; COLON; POOR;

D O I：

10.1016/j.ejca.2021.01.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in (V600EBRAF-)mutated ( BRAFmt) metastatic colorectal cancers (mCRCs) but no data are available about its prognostic impact in this setting. Methods: We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information. Tumours were dichotomized as synaptophysin high and low. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier and log-rank tests. Results: Thirty-five tumours (22.0%) showed any level of positivity for synaptophysin, and 18 (11.3%) were characterized by positivity in at least 20% of tumour cells. Four cases resulted 100% synaptophysin positive. The histotype of synaptophysin-positive tumours (i.e. >= 20%) was not otherwise specified in 11 cases (61.1%) and mucinous adenocarcinoma in 4 cases (22.2%). Four cases were DNA mismatch repair deficient (22.2%) and 7 (38.9%) were characterized by a high number of tumour-infiltrating lymphocytes. At multivariate analysis, high synaptophysin expression was a negative independent prognostic factor for both PFS (HR = 2.00, 95% confidence interval [CI] 1.21-3.33, p = 0.006) and OS (HR = 2.27, 95% CI 1.35-3.85, p = 0.001). Conclusions: Among BRAFmt mCRCs, synaptophysin-positive tumours are characterized by worse PFS and OS. Further studies should investigate the molecular mechanisms involved in the acquisition of the neuroendocrine phenotype to identify novel-targeted treatment strategies. (C) 2021 Elsevier Ltd. All rights reserved.

引用

页码：145 / 154

页数：10

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