PTEN deletion is rare but often homogeneous in gastric cancer

Mina, Sormeh; Bohn, Benjamin A.; Simon, Ronald; Krohn, Antje; Reeh, Matthias; Arnold, Dirk; Bokemeyer, Carsten; Sauter, Guido; Izbicki, Jakob R.; Marx, Andreas; Stahl, Phillip

doi:10.1136/jclinpath-2011-200525

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…2). A previous study also found that PTEN deletion was often homogeneous in gastric cancer [24]. Given the homogeneous distribution of PTEN-negative cells in GEA, evaluation of PTEN expression in a biopsy specimen will likely be a reliable method for evaluation of PTEN loss.…”

Section: Discussionmentioning

confidence: 86%

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PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma

et al. 2016

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Background Although trastuzumab improves the outcome of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing gastric or gastroesophageal junction adenocarcinoma (collectively referred to as ''gastroesophageal adenocarcinoma''; GEA), no clinical response is observed in a substantial population of patients. A predictive biomarker of trastuzumab response is required. The aim of this study was to evaluate whether the hyperactivation of the downstream phosphatidylinositol 3-kinase pathway, due to phosphatase and tensin homolog (PTEN) loss or PIK3CA mutations, could provide trastuzumab resistance in GEA. Methods Expression of HER2 and PTEN, and PIK3CA gene mutations were screened in 264 surgically resected GEA specimens. The effects of PTEN knockdown on the response to trastuzumab on cell viability, HER2 downstream signaling, apoptosis, and cell cycle were evaluated in HER2-overexpressing NCI-N87 gastric adenocarcinoma and OE19 esophageal adenocarcinoma cell lines. Inhibition of xenograft tumor growth by trastuzumab was investigated in OE19 cells with or without PTEN knockdown. The PTEN expression and objective response were analyzed in 23 GEA patients who received trastuzumab-based therapy.Results PTEN loss was identified in 34.5 % of HER2-overexpressing GEA patients, whereas PIK3CA mutations were rare (5.6 %). Trastuzumab-mediated growth suppression, apoptosis, and G 1 cell cycle arrest were inhibited by PTEN knockdown through Akt activation in NCI-N87 and OE19 cells. PTEN knockdown impaired the antiproliferative effect of trastuzumab in OE19 xenograft models. A clinical response was observed in 50 % of PTEN-positive tumors (9 of 18) but in no tumors with PTEN loss (none of 5). Conclusions PTEN loss was frequently found in HER2-overexpressing tumors, and was associated with a poor response to trastuzumab-based therapy in patients with GEA.

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Section: Discussionmentioning

confidence: 86%

“…However, some reports have shown that loss of PTEN expression or deletion of the PTEN gene is rarely found (3.7-5.3 %) in HER2-overexpressing gastric cancer [23,24]. The discrepancy in these results might be due to variations in the definition of PTEN loss.…”

Section: Discussionmentioning

confidence: 96%

PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma

et al. 2016

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“…To decrease the false‐positive rate, the literature recommends using centromeric probes as controls, as well as evaluation of a substantial number of cells . The usefulness of FISH in the evaluation of PTEN has been evaluated in carcinomas of the prostate, rectum, and stomach …”

Section: Discussionmentioning

confidence: 99%

FISH analysis ofPTENin endometrial carcinoma. comparison withSNParrays andMLPA

et al. 2014

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AimsTo check the usefulness of a standardized protocol of PTEN FISH in 31 endometrial carcinomas (ECs) in comparison with SNP array (SNPA), multiplex ligation-dependent probe amplification (MLPA), and immunohistochemistry.Methods and resultsFluorescence in-situ hybridization analysis showed two PTEN copies in 17 cases, three copies in nine cases, hemizygous deletion in two cases, and diverse cell populations with different PTEN copy number in three cases. A good correlation was seen between FISH and SNPA, particularly in cases with three copies. FISH identified two cases with entire deletion of chromosome 10, but did not identify a focal deletion of PTEN. Five cases with PTEN deletion and duplication of the second allele by SNPA were interpreted as normal by FISH. Concordance between FISH and MLPA was seen in 15 cases with two copies, and in two cases with PTEN deletion. Six cases were interpreted as amplified by MLPA, but showed polyploidy by FISH. FISH was superior to SNPA and MLPA in assessing the tumours with diverse cell populations with different PTEN copies.ConclusionsThe results show good concordance between FISH, SNPA and MLPA. SNPA was superior in tumours with deletion of one copy and duplication of the second allele. FISH was superior in assessing tumour heterogeneity.

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“…The functional loss of PTEN by deletions or mutations may therefore promote tumour genesis. Deletions and mutations of PTEN have been described in more than 30 tumour types . In several cancer types, including prostate, gastric and ovarian cancers, PTEN deletions were linked to unfavourable disease course.…”

Section: Introductionmentioning

confidence: 99%

PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer

et al. 2013

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PTEN deletion is rare but often homogeneous in gastric cancer

Abstract: Genomic PTEN deletion is a rare event in gastric adenocarcinoma but correlates with metastatic disease. The homogeneous distribution pattern indicates that this alteration occurs early in tumour development.

Cited by 16 publications

References 43 publications

PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma

PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma

FISH analysis ofPTENin endometrial carcinoma. comparison withSNParrays andMLPA

PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer

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