Analysis of PTEN expression in the large intestine polyps and its relation to the recognized histopathological and clinical risk factors for cancer development in this location.

Współczesna Onkologia 2012, Aug;16(4):310-315.

 

Dariusz Waniczek1, Mirosław Śnietura2, Wojciech Pigłowski2, Jerzy Rdes3, Agnieszka Kopeć2, Joanna Młynarczyk-Liszka2Marek Rudzki1, Krystyna Hudyka1, Dariusz Lange2 , Jerzy Arendt1

1 Medical University of Silesia, Chair and Departament of General and Gastrointestinal Surgery, Bytom

2 Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Pathology Department

Medical University of Silesia, Department of Health Economics

 

Key words

PTEN, colorectal polyp, colorectal cancer, familial adenomatous polyposis, cancer transformation

 

Abstract

BACKGROUND: PTEN is an important gene whose protein product is double specific phosphatase holding key regulatory functions in sending signals from membrane receptors for growth factors into the cell downstreams. Besides the influence on proliferation and apoptosis, it also regulates angiogenesis. Its participation mainly processes by PI3K/AKT signaling pathway in the pathomechanism of many malignant cancers was unambiguously confirmed.

The PTEN function gets disturbed on many levels and for various reasons; starting from a wide range of mutations, through epigenetic changes such as hypermethylation, oxidation switch off, and finishing with an increased protein degradation. Disorders of PTEN protein expression seem to be even more common in many carcinomas.

The aim of the study is to enquire the meaning of PTEN expression in the cancer transformation process in  large intestine glandular polyps.

METHODS: The group includes 40 patients, 21 men and 19 women, age median 64 years (51-83) qualified to endoscopic removal of large intestine polyp. Tissue material obtained during polyp removal endoscopy was immediately fixed in 4% buffered formalin  solution with the mixture of phosphatase activity inhibitors (PhosStop Roche).  Time of fixation 24-48h. After fixation, the material was embedded in paraffin. PTEN visualization was based on specific rabbit monoclonal antibodies (Cell Signaling).  The expression of PTEN protein in large intestine and rectum polyps was marked by a semi-quantitative method and an attempt to correlate the results  with the acknowledged clinical and histopathological malignancy risk factors was undertaken.

RESULTS: Loss or weakening of protein expression was found in 45% cases. Moreover, the relationship between polyp diameter and a loss of PTEN expression was proved.

CONCLUSION: The received results can indicate a significant participation of PTEN gene in early oncogenesis stages of large intestine cancer.

 

Supplementary text

Average polyp diameter including foci without PTEN protein expression was 25mm, while polyps showing decreased expression of this protein had the mean diameter of 11.1mm.  The polyps of normal PTEN expression were the smallest, their diameter was 6.2mm.

In case of  adenomatous polyps the loss of PTEN function may be a sign of precancerous state – cancer transformation.

 

Dariusz Waniczek-1

Focal decrease and loss of PTEN protein (see arrows) in glandular polyp. Anti PTEN immunohistochemical staining, original  magnification 10x.

 

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