LOSS OF EXPRESSION OF THE TUMOR SUPPRESSOR KLOTHO IN CERVICAL CARCINOMA

Sarit Aviel-Ronen 1,2 Tamar Rubinek 3 Oranit Zadok 1 Aya Vituri 4 Camila Avivi 1 Ido Wolf 3,5 Iris Barshack 1,5
1Pathology, Sheba Medical Center, Tel Hashomer
2Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer
3Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv
4Statistics and Operations Research, Tel Aviv University, Tel Aviv
5Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv

Background: Klotho is an anti aging gene with recognized tumor suppressor function in breast and gastric cancer. Very little is known about its role in cervical carcinoma.

Objective: To study the expression of klotho in cervical carcinoma at the protein and mRNA levels by immunohistochemistry (IHC) and RT-PCR.

Materials and Methods: We have collected 82 samples from 44 squamous cell carcinoma (SQCC) patients and 38 adenocarcinoma (ADC) patients and reviewed the pathological diagnosis. All samples were formalin-fixed paraffin embedded (FFPE) and were stained for klotho by IHC. Staining was scored for percentage of stained cells and intensity and tumor staining was compared to that of normal adjacent tissue. mRNA was extracted from 18 FFPE samples, chosen for their differential IHC expression of klotho, and the level of klotho mRNA was studied by RT-PCR.

Results: Altogether 9 out of 82 (10.9%) cervical carcinoma samples were negative for klotho IHC. In ADC 7 out of 38 samples (18.4%) were negative for klotho IHC staining, while in SQCC 2 out of 44 samples (4.5%) were negative. Normal adjacent tissue was positively stained for klotho in all the samples. Statistical analysis showed that IHC expression was significantly lower in ADC compared to SQCC (p=0.0235) and that both ADC and SQCC had reduced expression compared to normal adjacent tissue (p< 0.001, p= 0.0476 respectively). Initial RT-PCR results show that the reduction in klotho expression is also present at the mRNA level.

Conclusions: We have found that klotho expression is lost in ~10% of cervical carcinoma cases, more in ADC than in SQCC. Further investigation is required to find the molecular mechanism responsible for this tumor suppressor gene loss of function.








 




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