Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: Results from studies of the NCIC Clinical Trials Group (NCIC CTG)

Mackay, Helen; Gallinger, Steven; Tsao, Ming‐Sound; McLachlin, C. Meg; Tu, Dongsheng; Keiser, Katharina; Eisenhauer, Elizabeth; Oza, Amit M.

doi:10.1016/j.ejca.2010.02.031

Cited by 82 publications

(66 citation statements)

References 27 publications

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“…Similar results were previously reported in endometrial cancer [20], colorectal cancer [21], breast cancer [22], bronchioloalveolar carcinoma and lung adenocarcinoma [23]. Also, PTEN expression in stomach cancer in this study was inversely correlated with tumor size and tumor stage which agreed with previous studies in colorectal carcinoma [21].…”

Section: Discussionsupporting

confidence: 94%

Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer

Yang

et al. 2011

Pathol. Oncol. Res.

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Cancer stem cells are nowadays considered to be the origin of cancer. Also, stem cell associated genes are emerging as predictors of cancer malignancy. We investigated the association of several stemness genes (c-Myc, PTEN, p57 and p21) with clinic pathological parameters and survival in stomach cancer by performing immunohistochemistry on paraffin sections of gastric cancer patients who underwent surgical staging with following-up statistics. We discovered that expression of c-Myc was significantly related to distant metastasis, the combined expression of PTEN and p21 correlated positively to overall survival, while p57 was less useful in overall survival prediction in gastric cancer. Additionally, there is a positive correlation between expressions of p57 and p21. In conclusion, our present study indicated that expression of stemness genes (c-Myc, PTEN, p57 and p21) performed different predictive potential in the evaluation of clinical malignancy levels in gastric cancer.

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Section: Discussionsupporting

confidence: 94%

Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer

Yang

et al. 2011

Pathol. Oncol. Res.

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“…Some studies reported that microsatellite instability is associated with a favorable prognosis, 31,32 whereas in other studies a significant worse prognosis was found. 33,34 Possible explanations for these discrepancies include cohort differences, lack of statistical power, and diversity of methodology. Further studies will be required to clarify the effects of POLE mutations and microsatellite instability on the biological behavior of endometrial tumor cells and the associated mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

et al. 2015

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This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P = 0.014) and distant metastasis rates 23%, 64%, and 50% (P = 0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n = 14) and group 2 (microsatellite instable; n = 19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n = 36) and 39% in group 4 (NSMP; Po 0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; Po 0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment. Modern Pathology (2015) 28, 836-844; doi:10.1038/modpathol.2015 published online 27 February 2015 Risk classification of endometrial carcinomas is based upon a combination of clinical and histopathological factors and is used in guiding adjuvant therapy. High-risk factors are (combinations of) advanced age, high-grade, non-endometrioid histology, extensive lymphovascular space invasion, and

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“…A high incidence of PTEN mutations (26-80% in different series) has been identified in endometrial cancer (EC) and is associated to worst prognosis [142]. This finding served as the rationale for a two-stage, phase II study of singleagent temsirolimus 25 mg IV weekly in women with chemotherapy naïve, recurrent or metastatic EC.…”

Section: Endometrial Cancermentioning

confidence: 98%

Clinical activity of mammalian target of rapamycin inhibitors in solid tumors

et al. 2011

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The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway is vital for cell metabolism, growth, and proliferation. mTOR is frequently upregulated in many tumor types and hence has become an important target in cancer treatment. Sirolimus and its derivatives (rapalogs) interact with the intracellular receptor FK506 binding protein 12 (FKBP12), forming a complex with high affinity for mTOR and thus disrupting its activity. Rapalogs are being evaluated extensively in cancer patients with different formulations and schedules. Significant clinical activity has led to their approval for the treatment of kidney cancer, mantle cell lymphoma, and subependymal giant cell astrocytoma; however, despite increasing knowledge about cancer cell biology, their activity in other malignancies is unclear. Further research is needed to identify optimal dosage, administration and targeted combination as well as the subset of patients likely to respond to mTOR/PI3K inhibition. This review focuses on a discussion of the pathway, its implications in cancer biology and results of clinical trials of rapalogs alone or in combination, organizing them by common malignancy type.

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Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: Results from studies of the NCIC Clinical Trials Group (NCIC CTG)

Cited by 82 publications

References 27 publications

Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer

Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

Clinical activity of mammalian target of rapamycin inhibitors in solid tumors

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