title: Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel Hashomer, Israel Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Aviel-Ronen
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Rubinek
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Oranit
authors.initials: O
authors.lastname: Zadok
authors.affiliation: Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: Aya
authors.initials: A
authors.lastname: Vituri
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Wolf
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D000090265:Klotho Proteins; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: CERVICAL CANCER; GYNAECOLOGICAL PATHOLOGY; IMMUNOHISTOCHEMISTRY