The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma

• Published in: Histopathology Vol. 50; no. 3; pp. 338 - 347
• Main Authors: Mylona, E, Nomikos, A, Magkou, C, Kamberou, M, Papassideri, I, Keramopoulos, A, Nakopoulou, L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2007; Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor; breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - enzymology; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - secondary; Female; Fluorescent Antibody Technique, Indirect; gelatinase B; Gynecology. Andrology. Obstetrics; Humans; Immunoenzyme Techniques; immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Lymph Nodes - pathology; Mammary gland diseases; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Middle Aged; MMP-14; MMP-9; MT1-MMP; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PPAR gamma - metabolism; Prognosis; Receptor, ErbB-2 - metabolism; Survival Rate; Tumors; Immunohistochemistry; Prognosis; Enzyme; MMP-14; Metalloendopeptidases; Breast cancer; Malignant tumor; Gelatinase B; Mammary gland diseases; Peptidases; Breast carcinoma; Anatomic pathology; MT1-MMP; Hydrolases; Localization; MMP-9; Interstitial collagenase
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2007.02615.x

Aims:  To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c‐erbB2 and peroxisome proliferator‐activated receptor (PPAR) gamma. Methods:  Immunohistochemistry was carried out on 175 paraffin‐embedded breast tissue specimens to detect MT1‐MMP, MMP‐9, oestrogen receptor (ER), progesterone receptor, c‐erbB‐2, Ki67, topoisomerase IIα (topo IIα) and PPARγ protein expression. Results:  Both MT1‐MMP and MMP‐9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1‐MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIα (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1‐MMP was positively associated with MMP‐9 (P = 0.010) and PPARγ (P < 0.0001). Cytoplasmic MMP‐9 was inversely associated with Ki67 (P = 0.034) and topo IIα (P = 0.004), whereas its relationship with MT1‐MMP (P = 0.034) and PPARγ (P = 0.024) was found to be positive. Stromal MMP‐9 was more often observed in c‐erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse‐free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). Conclusions:  Cytoplasmic MT1‐MMP and MMP‐9 seem to be related to well‐differentiated tumours, with a low proliferation potential, while stromal MMP‐9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.