Publications

Authors:

Ferrara, Miriam Grazia; Martini, Maurizio; D'Argento, Ettore; Forcella, Chiara; Vita, Emanuele; Di Noia, Vincenzo; Sperduti, Isabella; Bilotta, Mirna; Ribelli, Marta; Damiano, Paola; Cannella, Antonella; Stefani, Alessio; Pilotto, Sara; Carbone, Carmine; Piro, Geny; Milella, Michele; Tortora, Giampaolo; Bria, Emilio

Title:

PTEN Loss as a Predictor of Tumor Heterogeneity and Poor Prognosis in Patients With EGFR-mutant Advanced Non-small-cell Lung Cancer Receiving Tyrosine Kinase Inhibitors

Year:

2021

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

No

Name of journal:

CLINICAL LUNG CANCER

ISSN of journal:

1525-7304

N° Volume:

22

Number or Folder:

4

Page numbers:

351-360

Keyword:

Afatinib; Erlotinib; Gefitinib; IGFR; MET; Osimertinib; p53; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Disease Progression; ErbB Receptors; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Mutation; PTEN Phosphohydrolase; Prognosis; Progression-Free Survival; Protein Kinase Inhibitors; Reproducibility of Results; Retrospective Studies; Survival Rate

Short description of contents:

Background: Rapid disease progression of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has been recently associated with tumor heterogeneity, which may be mirrored by coexisting concomitant alterations. The aim of this analysis was to investigate the correlation between loss of function of PTEN and the efficacy of tyrosine kinase inhibitors in this population. Materials and Methods: Archival tumor blocks from patients with EGFR-mutant NSCLC who were administered upfront tyrosine kinase inhibitors were retrospectively collected. The status of 4 genes (PTEN, TP53, c-MET, IGFR) was evaluated by immunohistochemistry, and it was correlated with overall response rate, overall survival (OS), and progression-free survival (PFS). Results: Fifty-one patients were included. In multivariate analysis, PTEN loss (hazard ratio [HR], 3.46; 95% confidence interval [CI], 1.56-7.66; P = .002), IGFR overexpression (HR, 2.22; 95% CI, 1.03-4.77; P = .04), liver metastases (HR, 3.55; 95% CI, 1.46-8.65; P = .005), and Eastern Cooperative Oncology Group performance status (ECOG PS) > 1 (HR, 2.57; 95% CI, 1.04-6.34; P = .04) were significantly associated with shorter PFS. Patients with PTEN loss had a median PFS of 6 months (2-year PFS, 11.6%), whereas patients without PTEN loss had a median PFS of 18 months (2-year PFS, 43.6%) (log-rank P < .005). In the multivariate analysis, PTEN loss (HR, 5.92; 95% CI, 2.37-14.81; P < .005), liver metastases (HR, 2.63; 95% CI, 1.06-6.51; P = .037), and ECOG PS > 1 (HR, 2.80; 95% CI, 1.15-6.81; P = .024) were significantly associated with shorter OS. Patients with PTEN loss had a median OS of 6 months (2-year OS, 12.2%), whereas in patients without PTEN loss, OS was not reached (2-year OS, 63.9%) (log-rank P < .0005).Conclusions: A low-cost and reproducible immunohistochemistry assay for PTEN loss analysis represents a potential tool for identifying tumor heterogeneity in patients with advanced EGFR-mutant NSCLC.

Product ID:

126255

Handle IRIS:

11562/1063754

Last Modified:

November 17, 2022

Bibliographic citation:

Ferrara, Miriam Grazia; Martini, Maurizio; D'Argento, Ettore; Forcella, Chiara; Vita, Emanuele; Di Noia, Vincenzo; Sperduti, Isabella; Bilotta, Mirna; Ribelli, Marta; Damiano, Paola; Cannella, Antonella; Stefani, Alessio; Pilotto, Sara; Carbone, Carmine; Piro, Geny; Milella, Michele; Tortora, Giampaolo; Bria, Emilio, PTEN Loss as a Predictor of Tumor Heterogeneity and Poor Prognosis in Patients With EGFR-mutant Advanced Non-small-cell Lung Cancer Receiving Tyrosine Kinase Inhibitors «CLINICAL LUNG CANCER» , vol. 22 , n. 4 , 2021 , pp. 351-360

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