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Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma
  1. Sarit Aviel-Ronen1,2,
  2. Tami Rubinek3,
  3. Oranit Zadok1,
  4. Aya Vituri4,
  5. Camila Avivi1,
  6. Ido Wolf3,5,
  7. Iris Barshack1,5
  1. 1Department of Pathology, Sheba Medical Center, Tel Hashomer, Israel
  2. 2Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer, Israel
  3. 3Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel
  4. 4Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv-Yafo, Israel
  5. 5Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel
  1. Correspondence to Dr Sarit Aviel-Ronen, Department of Pathology, Sheba Medical Center, Tel Hashomer 52621, Israel; saritaviel{at}


Aims Klotho is a trans-membrane protein that serves as a tumour suppressor in a wide array of malignancies. Recent data suggest it as an epigenetically silenced tumour suppressor in cervical cancer. Yet, the expression pattern of klotho in cervical cancer has not been determined. We aimed to study the expression of klotho in squamous cell carcinomas (SQCC) and adenocarcinoma (ADC) of the cervix.

Methods Klotho expression was analysed by immunohistochemistry in 44 SQCC samples, 38 ADC samples and the adjacent normal tissue. For each sample, percentage of positive stained cells, staining intensity and a combined staining score were recorded. Staining was validated by measuring klotho mRNA levels, using quantitative RT-PCR, in 18 of the samples.

Results Klotho expression was high in all endocervical and exocervical normal tissues adjacent to tumour. No expression of klotho was noted in 7 out of 38 (18.4%) ADC samples and in 2 out of 44 (4.5%) SQCC samples. Staining intensity, number of positively stained cells and combined intensity score were all lower in tumours compared with normal adjacent tissues in ADC and SQCC. Klotho mRNA levels highly correlated with immunohistochemical (IHC) staining (p=0.008).

Conclusions We found reduced klotho expression in cervical carcinoma, especially in ADC, compared with normal adjacent tissue. Our results support the role of klotho as a potential tumour suppressor in cervical cancer. Further studies are required in order to establish the therapeutic role of klotho in cervical carcinoma and identify patients who may benefit from it.


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