Increased expression of calpain 6 during the progression of uterine cervical neoplasia: immunohistochemical analysis.

Calpain 6 (Capn6) is one of the calcium-dependent intracellular nonlysosomal proteases and is known for tissue-specific expression, primarily in the placenta. We investigated whether the expression of Capn6 is associated with the progression of uterine cervical neoplasia. We analyzed 81 formalin-fixed paraffin-embedded cervical tissues that included six normal cervical epithelium, 20 low-grade squamous intraepithelial lesions (LSIL), 17 high-grade squamous intraepithelial lesions (HSIL), 20 invasive squamous cell carcinomas (ISCC) without lymph node (LN) metastasis and 18 ISCCs with LN metastasis. The expression of Capn6 was determined by immunohistochemistry and was undetectable in normal cervical squamous epithelium. The expression of the protein gradually increased in accordance with the progression from normal to LSIL (P=0.000) and from LSIL to HSIL (P=0.003). Capn6 was detected in all cases of ISCC. However, there was no significant difference between HSIL and ISCC (P=0.945), ISCC with LN metastases and ISCC without LN metastases (P=0.862). The distribution of staining was diffuse. The cytoplasm and nucleus were stained evenly. These results suggest that Capn6 may play a significant role in the development of LSIL and may also function in the progression of LSIL to HSIL. However, its role in tumor development and metastases is not clear.

[1]  H. Aburatani,et al.  Calpain 6 Is Involved in Microtubule Stabilization and Cytoskeletal Organization , 2007, Molecular and Cellular Biology.

[2]  D. Bae,et al.  Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis , 2006, International Journal of Gynecologic Cancer.

[3]  A. Skubitz,et al.  Differential gene expression in leiomyosarcoma , 2003, Cancer.

[4]  D. E. Goll,et al.  The calpain system. , 2003, Physiological reviews.

[5]  A. Skubitz,et al.  Differential gene expression in uterine leiomyoma. , 2003, The Journal of laboratory and clinical medicine.

[6]  J. T. Cox,et al.  Management of precursor lesions of cervical carcinoma: history, host defense, and a survey of modalities. , 2002, Obstetrics and gynecology clinics of North America.

[7]  N. Carragher,et al.  Calpain: a role in cell transformation and migration. , 2002, The international journal of biochemistry & cell biology.

[8]  T. Boehm,et al.  Identification and characterization of two novel calpain large subunit genes. , 2001, Gene.

[9]  M. von Knebel Doeberitz,et al.  Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri , 2001, International journal of cancer.

[10]  H. Hollema,et al.  Telomerase in (pre)neoplastic cervical disease. , 2000, Human pathology.

[11]  F. X. Bosch,et al.  Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  R. Ashfaq,et al.  Allelic loss and microsatellite alterations of chromosome 3p14.2 are more frequent in recurrent cervical dysplasias. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  T. Boehm,et al.  Genomic organization of mouse Capn5 and Capn6 genes confirms that they are a distinct calpain subfamily. , 1998, Genomics.

[14]  K. Suzuki,et al.  Structure and physiological function of calpains. , 1997, The Biochemical journal.

[15]  M. Vingron,et al.  A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. , 1997, Genomics.

[16]  A. Östör,et al.  Natural history of cervical intraepithelial neoplasia: a critical review. , 1993, International Journal of Gynecological Pathology.

[17]  R. Richart.  A modified terminology for cervical intraepithelial neoplasia. , 1990, Obstetrics and gynecology.

[18]  P. Bartels,et al.  DNA ploidy profiles as prognostic indicators in CIN lesions. , 1989, American journal of clinical pathology.

[19]  J. Cuzick,et al.  PROGRESSIVE POTENTIAL OF MILD CERVICAL ATYPIA: PROSPECTIVE CYTOLOGICAL, COLPOSCOPIC, AND VIROLOGICAL STUDY , 1986, The Lancet.