Potential for Predicting Lymph-node Metastasis in Invasive Breast Carcinoma of No Special Type Using MT1-MMP Immunohistochemistry Staining
DOI:
https://doi.org/10.3889/oamjms.2023.9939Keywords:
Membrane-type 1-matrix metalloproteinase, Breast cancer, Immunohistochemistry, Metastasis, Lymph-nodeAbstract
BACKGROUND: Lymph-node metastasis (LNM) is the most frequent complication of invasive breast carcinoma (IBC).
AIM: Using immunohistochemistry (IHC), this study aims to determine the role of membrane-type 1-matrix metalloproteinase (MT1-MMP) expression as a biomarker for LNM in IBC of no special type (IBC-NST).
MATERIALS AND METHODS: Primary tumors from individuals with IBC-NST were preserved in paraffin and then categorized as having LNM or not. Tumor size, lymphovascular invasion (LVI), tumor grade, MT1-MMP expression, and other factors were evaluated across a range of ages. MT1-MMP expression was assessed by IHC, with supplemental data acquired from archives. Collecting and analyzing the data required the use of both bivariate and multivariate techniques.
RESULTS: The odds ratio (OR) for LNM was 5.003 (95% CI: 1.68–20.61) for MT1-MMP expression, while the OR for LVI was 4.71 (95% CI: 1.57–18.8). These associations were found using the Firth penalized likelihood Logit analysis method. At an H-score cutoff of 202.22 (70.8% sensitivity and 95.8% specificity), an area under the receiver operating characteristic of 0.9130.038 (95% CI: 0.838–0.989) was found for MT1-MMP expression in diagnosing LNM.
CONCLUSION: In conjunction with LVI, MT1-MMP expression may serve as a predictor of LNM. To further assist data separation in future research, the MT1-MMP expression H-score cutoff of 202.22 could be used.
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GLOBOCAN. Estimated Cancer Incidence, Mortality and Prevalence in 2018. France: International Agency for Research on Cancer-WHO; 2019. Available from: https://gco.iarc.fr/ today/data/factsheets/cancers/20-Breast-fact-sheet.pdf [Last accessed on 2019 Mar 22].
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660 PMid:33538338
Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020;77(2):181-5. https://doi. org/10.1111/his.14091 PMid:32056259
Ren L, Wang Y, Zhu L, Shen L, Zhang J, Wang J, et al. Optimization of a MT1-MMP-targeting peptide and its application in near- infrared fluorescence tumor imaging. Sci Rep. 2018;8(1):10334. https://doi.org/10.1038/s41598-018-28493-9 PMid:29985410
Cepeda MA, Pelling JJ, Evered CL, Williams KC, Freedman Z, Stan I, et al. Less is more: Low expression of MT1-MMP is optimal to promote migration and tumourigenesis of breast cancer cells. Mol Cancer. 2016;15(1):65. https://doi.org/10.1186/s12943-016-0547-x PMid:27756325
Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mason MD, et al. Expression of membrane Type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med. 2006;17(4):583-90. PMid:16525713
Rickham PP. Human experimentation. Code of ethics of the world medical association. Declaration of Helsinki. Br Med J. 1964;2(5402):177. https://doi.org/10.1136/bmj.2.5402.177 PMid:14150898
Hashimoto K, Tsuda H, Koizumi F, Shimizu C, Yonemori K, Ando M, et al. Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple- negative breast cancer. Ann Oncol. 2014;25(10):1973-9. https://doi.org/10.1093/annonc/mdu247 PMid:25009009
O’Brien J, Hayder H, Peng C. Automated quantification and analysis of cell counting procedures using imageJ plugins. J Vis Exp. 2016;117:54719. https://doi.org/10.3791/54719 PMid:27911396
Choudhury KR, Yagle KJ, Swanson PE, Krohn KA, Rajendran JG. A robust automated measure of average antibody staining in immunohistochemistry images. J Histochem Cytochem. 2010;58(2):95-107. PMid:19687472
Koo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med.
;15(2):155-63. https://doi.org/10.1016/j.jcm.2016.02.012 PMid:27330520
Ma H, Lu Y, Marchbanks PA, Folger SG, Strom BL, McDonald JA, et al. Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women. Breast Cancer Res. 2013;15(5):R90. https://doi.org/10.1186/bcr3486 PMid:24070170
Wang X. Firth logistic regression for rare variant association tests. Front Genet. 2014;5:187. https://doi.org/10.3389/fgene.2014.00187 PMid:24995013
Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010;5(9):1315-6. https://doi.org/10.1097/JTO.0b013e3181ec173d PMid:20736804
Ruopp MD, Perkins NJ, Whitcomb BW, Schisterman EF. Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection. Biom J. 2008;50(3):419-30. https://doi.org/10.1002/bimj.200710415 PMid:18435502
Kallner A. Formulas. In: Kallner A, editor. Laboratory Statistics. 2nd ed. Netherlands: Elsevier; 2018. p. 1-140.
Pahwa S, Stawikowski MJ, Fields GB. Monitoring and inhibiting MT1-MMP during cancer initiation and progression. Cancers (Basel). 2014;6(1):416-35. https://doi.org/10.3390/cancers6010416 PMid:24549119
Li Y, Cai G, Yuan S, Jun Y, Li N, Wang L, et al. The overexpression membrane Type 1 matrix metalloproteinase is associated with the progression and prognosis in breast cancer. Am J Transl Res. 2015;7(1):120-7. PMid:25755834
Hasan A, Youssef A. Infiltrating duct carcinoma of the breast; histological difference between the primary and the axillary nodal metastasis. Rev Senol Patol Mamar. 2021;34(1):17-22. https://doi.org/10.1016/j.senol.2020.09.003
Maquoi E, Assent D, Detilleux J, Pequeux C, Foidart JM, Noël A. MT1-MMP protects breast carcinoma cells against Type I collagen-induced apoptosis. Oncogene. 2012;31(4):480-93. https://doi.org/10.1038/onc.2011.249 PMid:21706048
Melzer C, von der Ohe J, Hass R. Breast carcinoma: From initial tumor cell detachment to settlement at secondary sites. Biomed Res Int. 2017;2017:8534371. https://doi.org/10.1155/2017/8534371 PMid:28785589
Perentes JY, Kirkpatrick ND, Nagano S, Smith EY, Shaver CM, Sgroi D, et al. Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors. Cancer Res. 2011;71(13):4527-38. https://doi.org/10.1158/0008-5472.CAN-10-4376 PMid:21571860
Nathanson SD, Kwon D, Kapke A, Alford SH, Chitale D. The role of lymph node metastasis in the systemic dissemination of breast cancer. Ann Surg Oncol. 2009;16(12):3396-405. https://doi.org/10.1245/s10434-009-0659-2 PMid:19657697
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Copyright (c) 2023 Primariadewi Rustamadji, Elvan Wiyarta, Kristina Anna Bethania (Author)
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