c-Met overexpression in breast cancer with positive axillary lymph node
Keywords:Breast cancer, c-Met overexpression, Positive axillary lymph node
Background: Breast cancer is the second most common cancer in the world and is the most epidemic cancer in women, with approximately 1.67 million cases. Metastasis of tumor cells to other organs is a major cause of the increasing trend of mortality in breast cancer. This study aims to analyze the expression of c-Met associated with metastasis to axillary lymph nodes in invasive breast cancer.
Method: The research was conducted at the Laboratory of Anatomical Pathology of Hasanuddin University Hospital. Stratified sampling was performed from January 2014 - January 2019. Immunohistochemical staining technique was applied upon 66 collected samples, followed by evaluating the c-Met expression score in invasive breast cancer group with positive and negative lymph node status.
Result: c-Met overexpression was found among the invasive breast cancer incidence with lymph node metastasis. Among 50 cases with c-Met overexpression (c-Met positive), 40 cases (80%) of invasive breast cancer with lymph node metastasis were identified, while 10 cases (20%) were found in invasive breast cancer without metastasis to lymph nodes. On 16 cases with negative c-Met, 3 cases (18.8%) were found in invasive breast cancer with lymph node metastasis, and 13 cases (81.3%) in invasive breast cancer without metastasis to the lymph nodes. The statistical test results indicated a significant correlation between c-Met expression scores and metastasis to axillary lymph nodes in invasive breast cancer (p <0.001).
Conclusion: As one of biomarkers, c-Met overexpression plays a vital role in the treatment of patients with invasive breast cancer to predict patient outcomes and to determine modalities. It is possible to apply c-Met overexpression to investigate aggressiveness of metastatic tumor cells in the future.
IARC ‘Latest world cancer statistics Global cancer burden rises to 14 . 1 million new cases in 2012 : Marked increase in breast cancers must be addressed Latest world cancer statistics Global cancer burden rises to 14 . 1 million new cases in 2012 : Marked incr’, Dec 2013:1-3.
Kementrian Kesehatan RI. Situasi kesehatan reproduksi remaja. Jakarta: Pusat Data dan Informasi Kemenkes RI. 2015.
Zhao X, Qu J, Hui Y, Zhang H, Sun Y, Liu X, et al. Clinicopathological and prognostic significance of c-Met overexpression in breast cancer. Oncotarget. 2017 Aug 22;8(34):56758.
Sophia Ran,1 Lisa Volk, Kelly Hall, and Michael J. Flister. Lymphangiogenesis and Lymphatic Metastasis in Breast Cancer, Pathophysiology. 2010 Sep; 17(4): 229-51.
Ghoussoub RA, Dillon DA, D'Aquila T, Rimm EB, Fearon ER, Rimm DL. Expression of c‐met is a strong independent prognostic factor in breast carcinoma. Cancer: Interdisciplinary Int J Am Cancer Society. 1998 Apr 15;82(8):1513-20.
Elliott BE, Hung WL, Boag AH, Tuck AB. The role of hepatocyte growth factor (scatter factor) in epithelial mesenchymal transition and breast cancer. Canad J physiol pharmacol. 2002 Feb 1;80(2):91-102.
Ho-Yen CM, Jones JL, Kermorgant S. The clinical and functional significance of c-Met in breast cancer: a review. Breast Cancer Research. 2015 Dec;17(1):52.
Minuti G, Landi L. MET deregulation in breast cancer. Annals of translational medicine. 2015 Aug;3(13).
Parikh RA, Wang P, Beumer JH, Chu E, Appleman LJ. The potential roles of hepatocyte growth factor (HGF)-MET pathway inhibitors in cancer treatment. Onco Targets and therapy. 2014;7:969.
Watermann I, Schmitt B, Stellmacher F, Müller J, Gaber R, Kugler C, et al. Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?. Diagnostic pathol. 2015 Dec;10(1):130.
Rahman M, Mohammed S. Breast cancer metastasis and the lymphatic system. Oncology letters. 2015 Sep 1;10(3):1233-9.
Zagouri F, Brandstetter A, Moussiolis D, Chrysikos D, Dimitrakakis C, Tsigginou A. Low protein expression of MET in ER-positive and HER2-positive breast cancer. Anticancer research. 2014 Mar 1;34(3):1227-31.
Lengyel E, Prechtel D, Resau JH, Gauger K, Welk A, Lindemann K, et al. C‐Met overexpression in node‐positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. International J cancer. 2005 Feb 10;113(4):678-82.
Sennino B, Ishiguro-Oonuma T, Schriver BJ, Christensen JG, McDonald DM. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer research. 2013 Jun 15;73(12):3692-703.
Edakuni G, Sasatomi E, Satoh T, Tokunaga O, Miyazaki K. Expression of the hepatocyte growth factor/c‐Met pathway is increased at the cancer front in breast carcinoma. Pathol Int. 2001 Mar;51(3):172-8.
Spina A, De Pasquale V, Cerulo G, Cocchiaro P, Della Morte R, Avallone L, et al. HGF/c-MET axis in tumor microenvironment and metastasis formation. Biomedicines. 2015;3(1):71-88.