The role of the golgi phosphoprotein 2 in neoplastic lesions of the cervix uteri and comparison of that marker with human papillomavirus, p16 and ki-67

OBJECTIVE: Cervical cancer (CC) is identified as one of the most common types of cancer that causes cancer-related morbidity mortality, affecting many woman, worldwide. The Golgi Phosphoprotein 2 (GOLPH 2) gene is a type II transmembrane glycoprotein coded by the GOLM1 gene and weighs around 73 kilodaltons. This protein has been linked to the progression and aggressive nature of series of cancer types. We aimed to compare the use of GOLPH 2 expression with markers such as p16 and Ki-67 to classify and perform the differantial diagnosis of cervical precursor lesions. We also aimed to evalute the relationship between high risk human papillomavirüs (HR HPV) which has been identified as the major causal factor of CCs and cervical precursor lesions and GOLPH 2 protein which tends to increase usually during the course of viral infections and is linked to carcinogenesis. MATERIALS AND METHODS: A total of 116 cases including 19 cases identified as having nonneoplastic cervix (control), 22 with low-grade squamous intraepithelial lesions (LSIL; CIN I), 21 with high grade squamous intraepithelial lesion (HSIL; CIN II), 19 with high-grade squamous intraepithelial lesion (HSIL, CIN III) and 35 cases with cervical squamous cell carcinoma (SCC). Immunohistochemical staining using p16, Ki-67 and GOLPH 2 antibodies were applied to all cases. The signal paterns of the cases were researched using low risk HPV (LR HPV) and HR HPV in situ hybridization (ISH) techniques. Also, SCC cases were divided into three groups defined as well-differentiated (n=10 cases), moderately-differentiated (n=14), poorly-differentiated (n=11) and into two groups identified as early stage (n=13) and advanced stage (n=22). RESULTS: In our study, ''high'' GOLPH 2 expression rates were found as follows; 0 % in the control group, 0 % in the LSIL (CIN I) group, 33 % in the HSIL (CIN vi II) group, 52 % in the HSIL (CIN III) group and 91 % in the SCC group. ''High'' expression was seen in 71 (61.2%) cases using p16 and 44 (37.9%) cases with Ki-67. Twenty-two cases had positive staining with LR HPV ISH, and 18 had 0(15.5%), 3(2.6%) had episomal, 54(46.6%) had integrated and 41(35,3%) had mixed signaling patterns using HR HPV ISH. CONCLUSION: GOLPH 2, can be used as a marker along with p16 and Ki-67, for the diagnosis of cervical precursor lesions, and it was proven to be beneficial in the distinction of LSIL / HSIL and LSIL / SCC. Additionaly, our findings suggest that GOLPH 2 might have a role in the progression of cervical precursor lesions and cervical carcinogenesis. ''High'' levels of GOLPH 2 expression observed in advanced stage SCCs may reflect its possible connection to the aggression of the tumor and its significance in the prognosis. Although a significant relationship between HR HPV and SIL progression were determinated, similar results were not obtained with LR HPV. A significant correlation was observed between ''high '' GOLPH 2 expression and HR HPV infection, especially with the integrated signaling pattern of HR HPV. No relationship was observed between GOLPH 2 and SCC differentiation.