Expression of LIMS-1 Protein in Selected Cancers of the Genital Organ in Women
DOI:
https://doi.org/10.14205/2309-4400.2015.03.02.4Keywords:
Endometrial cancer, FIGO classification, LIMS-1 (PINCH-1), serous ovarian cancer, squamocellular cancer of uterine cervix.Abstract
Aim: The study aimed at immunohistochemical evaluation of LIMS-1 (PINCH-1-cysteine-histidine-rich) protein expression and localization in squamocellular cancer of uterine cervix, grades IB1 (T1b) and IIIB, in endometrial cancer, grades IB (T2b, NO, MO) and IIIB (T1, T2, T3, N1, MO) and in serous ovarian cancer, grades IB (pT1b) and IIIB (pT3b).
Methods: The immunohistochemical studies were conducted in paraffin sections, using rabbit polyclonal antibodies specific for LIMS-1 (SigmaR), diluted 1/200. The reaction was developed using EnVisionIM FLEX DAB+ Chromogen DAB solution. The expression was evaluated using modified IRS scale according to Remmele. Statistical analysis involved application of Kolmogonov–Smirnov test of normal distribution, Kruskall–Wallis test, analysis of K–means cluster and R-Spearman test.
Results: there was no relationship between the expression of LIMS-1 and the advancement of neoplastic disease according to FIGO classification in squamocellular cancer of uterine cervix: the significance coefficient in the chi-square test amounted to p = 0.086. In cases of endometrial cancer and ovarian cancer, the relationship between these variables showed the level of significance to be p = 0.045 and p = 0.041, respectively. In the cases where the chi-square test demonstrated a relationship between the stage of FIGO classification and the LIMS-1 expression, the R correlation coefficients of Spearman presented values of 0.66 (p=0.003) for endometrial cancer and 0.88 (p=0.005).
Conclusion: Increase in expression level of LIMS-1 protein in studied neoplasms was demonstrated to manifest positive correlation with degree of histological malignancy according to FIGO, or with neoplastic progression.
References
Tu Y, Li F, Goicoechea S, Wu C. The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. Mol Cell Biol 1999; 19: 2425-34. http://dx.doi.org/10.1128/MCB.19.3.2425
Lööf J, Rosell J, Bratthäll C, et al. Impact of PINCH expression on survival in colorectal cancer patients. BMC Cancer 2011; 11: 103. doi: 10.1186/1471-2407-11-103.
Rearden A. A new LIM protein containing an autoepitope homologous to senes cent cell antigen". Biochem Biophys Res Commun 1994; 201: 1124-31. http://dx.doi.org/10.1006/bbrc.1994.1822
Zhu ZL, Yan BY, Zhang Y, et al. PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Dis Markers 2012; 33: 171-8. doi: 10.3233/DMA-2012-0930.
Fukuda T, Chen K, Shi X, Wu C. PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J Biol Chem 2003; 278: 51324-33. http://dx.doi.org/10.1074/jbc.M309122200
Guo L, Wu C. Regulation of fibronectin matrix deposition and cell proliferation by the PINCH-ILK-CH-ILKBP complex. FASEB J 2002; 16: 1298-300. http://dx.doi.org/10.1096/fj.02-0089fje
Remmele W, Stegner HE. Vorschlag zur einheitlichen Definition eines immunoreaktiven Score (IRS) für den immunohistochemichen Östrogenrezeptor– Nachweis (ER– ICA) im Mammakarzinomgewebe. Pathologie 1987; 8: 138– 40.
Gao J, Arbman G, Rearden A, Sun X-F. Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. Neoplasia 2004; 6: 796-801. http://dx.doi.org/10.1593/neo.04304
Holmqvist A, Holmlund B, Ardsby M, Pathak S, Sun XF. PINCH expression in relation to radiation response in cocultured colon cancer cells and in rectal cancer patients. Oncol Rep 2013; 30: 2097-104. doi: 10.3892/or.2013.2673. Epub 2013 Aug 20.
Zhang HZ, Li XH, Zhang X, et al. PINCH protein expression in normal endometrium, atypical endometrial hyperplasia and endometrioid endometrial carcinoma. Chemotherapy 2010; 56: 291-7. doi: 10.1159/000319953. Epub 2010 Aug 11.
Knutsen A, Adell G, Sun X-F. Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy. Oncol Rep 2006; 16: 321-7. http://dx.doi.org/10.3892/or.16.2.321
Sun XF1, Zhang H. Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol Cancer 2006; 5: 43. http://dx.doi.org/10.1186/1476-4598-5-43
Chen K, Tu Y, Zhang Y, Blair H, Zhang L, Wu C. PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J Biol Chem 2008; 283: 2508-17. http://dx.doi.org/10.1074/jbc.M707307200
Lammering G, Taher MM, Gruenagel HH, Borchard F, Porschen R. Alterations in DNA ploidy status and cell proliferation induced by preoperative radiotherapy is a prognostic factor in rectal cancer. Clin Cancer Res 2000; 6: 3215-21.