کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4133292 1271414 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer
چکیده انگلیسی

SummaryColorectal cancer is the third most common malignancy worldwide. Anti–epidermal growth factor receptor (EGFR)–targeted therapy shows clinical evidence in this malignancy and improves outcome. The tumor suppressor gene phosphatase and tensin homologue (PTEN) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations (PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses (P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 44, Issue 8, August 2013, Pages 1524–1533
نویسندگان
, , , , , , , , , , , ,