Stella Maris Ranuncolo

PLASMA MMP-9 (92 kDa-MMP) ACTIVITY IS USEFUL IN THE FOLLOW-UP AND IN THE ASSESSMENT OF PROGNOSIS IN BREAST CANCER PATIENTS

Previously we determined that plasma MMP‐9 activity was significantly elevated in breast cancer patients compared to benign mammary pathologies and healthy controls. Now we analyzed its potential usefulness in the follow‐up and in the prognosis of these patients. MMP‐9 activity was measured by gelatin quantitative zymography in the euglobulin plasma fraction of 46 breast cancer patients in a 38‐month follow‐up study. Blood samples were obtained before surgery (S1), 1 month after (S2) and every 3 months. The relapse‐free survival (RFS) and overall survival (OS) analysis was performed along 56 months in 113 patients using the Kaplan‐Meier curves and Cox analysis. In 63% of the S2 analyzed, MMP‐9 decreased after surgery. In 44 patients evaluated during the adjuvant period who developed a complete response, MMP‐9 decreased compared to their S1, whereas 2 patients showed an enhancement in correlation with lack of response. Further analysis indicated that in all patients who never showed evidence of recurrence, plasma MMP‐9 activity remained low, but it increased 1 to 8 months preceding the clinical detection of progression in those patients who relapsed. Kaplan‐Meier curves indicated that high levels of plasma MMP‐9 activity at the moment of breast cancer diagnosis were associated with a worse OS rate. Cox analysis showed it was not associated with tumor stage or patients age. Our results, which show a good correlation between plasma MMP‐9 activity and the clinical status of each patient, suggest its usefulness as a marker both in the follow‐up and in the prognosis of breast cancer patients.

Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients

Matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa‐MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0–7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0–3.6) compared with the controls (Md 0.48 AU/ml, range 0.0–1.8). Patients with colon cancer or gliomas presented values of MMP‐9 similar to those of the healthy population. Multivariate analysis indicated that plasma MMP‐9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index. Lung cancer patients also presented high values of MMP‐9 (Md 1.43, range 0.0–3.6 [n = 26]), without association with tumor stage or histologic type. The levels of 92 kDa‐MMP activity in the plasma euglobulin fraction could be a potentially useful tumor marker in breast and lung cancer. Int. J. Cancer 89:389–394, 2000.

Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas.

Surgical cure of gliomas infiltrating into the brain is practically impossible and their clinical course is primarily determined by the biological behavior of the tumor cell. The purpose of this study was to analyze retrospectively prognostic input of p53, Mouse double minute-2 (Mdm2) and p16 in 103 uniformly treated patients with astrocytic tumors. The expression of these molecules was measured by immunohistochemical procedure. Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5–122) months for the survivors. We observed that 66% of gliomas showed mutated p53, while only 17% overexpressed Mdm2, the p53-regulatory molecule. Besides, almost 50% of gliomas lost p16 immunopositivity. Only p53 labeling showed a positive correlation with the grade of malignancy, according with the WHO classification. The association between mutated p53 and histological grade remained when prognostic variables were considered in a multivariate analysis. No association between p53 status and overall survival was found. On the other hand, Mdm2 overexpression and, unexpectedly, p16 immunopositivity were associated with a shorter survival in an univariate analysis. However, Cox-regression analysis showed that only Mdm2 in female patients was an independent prognostic factor, associated with shorter survival.In conclusion, our results suggest that Mdm2 could be a relevant marker in determining the evolution of glioma patients and could provide a more objective way to classify astrocytomas.

Circulating 92-kilodalton matrix metalloproteinase (MMP-9) activity is enhanced in the euglobulin plasma fraction of head and neck squamous cell carcinoma: Plasma 92-Kilodalton MMP Activity in HNSCC Tumors

Cancer lethality is usually the result of local invasion and metastasis of neoplastic cells from the primary tumor. Because of their ability to degrade extracellular matrix components (EMC), matrix metalloproteinases (MMPs) have been implicated in the breakdown of basement membranes and underlying stroma, thereby facilitating tumor growth and invasion.

Abstract 1577: Levels of Fibroblast Growth Factor 21 (FGF21) in serum as diagnostic biomarker in patients with breast cancer

Epidemiological studies have suggested a close link between obesity and breast cancer. There is an immediate need to investigate the potential pathways linking obesity and breast cancer to have an early diagnosis in patients and optimize the chance of cure. FGF21 is a regulator of local and systemic metabolic homeostasis and its expression is induced in response to diverse physiological or pathological stressors. High serum levels of FGF21 were found in obese individuals, subjects with metabolic syndrome, type 2 diabetes mellitus and coronary heart disease. Up to date, the clinical implication of FGF21 in cancer was not elucidated. Our aim was to study the role of serum FGF21 as a diagnostic biomarker of breast cancer. The serum levels of FGF21 in 45 breast cancer women patients (median age 59, range 32-88 years) and 51 age-matched healthy controls were evaluated using a quantitative ELISA test (RD SII: 17; SIII: 6; ND: 5] were obtained before surgery, without any previous treatment. We included patients with carcinoma in situ (n = 2), invasive ductal (n = 31) and lobular (n = 8), special carcinoma (n = 2), ND: 2. We observed that breast cancer patients showed significantly elevated values of serum FGF21 (median 224.55 pg/ml, range 24.15-776.19) respect to the levels observed in healthy controls (76.86, 0.00-425.60) (KW and MW, p Citation Format: Maria Elena Knott, Stella Maris Ranuncolo, Myriam Nunez, Eduardo Armanasco, Lydia Ines Puricelli, Mariana Silvia De Lorenzo. Levels of Fibroblast Growth Factor 21 (FGF21) in serum as diagnostic biomarker in patients with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2015-1577