Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinicopathological and biological factors in invasive breast cancer

Background: To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors. Methods: Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2. Results: Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p =0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042). Conclusions: Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cance

Joint tumor bud–MMP/TIMP count at the invasive front improves the prognostic evaluation of invasive breast carcinoma

Producción CientíficaBackground: Tumor budding is a histological phenomenon consisting of the formation of small clusters of one to five undifferentiated malignant cells detached from the main tumor mass which are observed in the tumor stroma. In the present study, we investigated the prognostic significance of tumor budding in breast cancer and its relationship with the expressions of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs). Methods: The number of buds was counted in whole-tissue sections from 153 patients with invasive ductal carcinomas who underwent a long follow-up period. In addition, an immunohistochemical study of MMP-9, -11, and -14 TIMP-1 and -2 expression by cell types at the invasive tumor front was carried out. Results: There was a wide variability in the number of buds among tumors, ranging from 0 to 28 (median = 5). Tumor budding count ≥ 4 was the optimal cut-off to predict both relapse-free and overall survival. High-grade tumor budding was associated with MMP/TIMP expression by cancer-associated fibroblasts. In addition, we found that the combination of tumor budding grade with MMP/TIMP expression by stromal cells, and especially with MMP-11 expression by mononuclear inflammatory cells, significantly improved the prognostic evaluation. Conclusion: High-grade tumor budding is associated with a more aggressive tumor phenotype, which, combined with MMP/TIMP expression by stromal cells at the invasive front of the tumor, identifies patients with poor prognosis.Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (grant PI17/02236 and DTS19-00109

Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer

<p>Abstract</p> <p>Background</p> <p>To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors.</p> <p>Methods</p> <p>Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2.</p> <p>Results</p> <p>Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042).</p> <p>Conclusions</p> <p>Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer.</p

Utilidad clínica de la determinación sérica del antígeno carbohidrato 195 (ca 195) en enfermedades digestivas

El antígeno carbohidrato 195 (ca195) es un antígeno asociado a tumor, identificado en altas concentraciones en el suero de pacientes con tumores digestivos. Está definido por el anticuerpo monoclonal cc3c195, el cual reconoce las formas sialatada y no sialatada del grupo sanguíneo lewis a. Hemos estudiado el comportamiento y utilidad clínica de este marcador, cuantificando los niveles séricos mediante un método radioinmunometrico (irma), de hybritech (usa), en 1637 sujetos distribuidos en: 101 controles (donantes de sangre), 631 con procesos benignos y 905 con tumores digestivos, con un total de 3027 determinaciones. Nuestros resultados han sido: a) tras el estudio del grupo control, hemos establecido el límite superior de normalidad en 12 u/ml, que corresponden al 97,5 percentil. No se han detectado diferencias significativas en función del sexo ni del habito tabáquico; b) en los pacientes con procesos benignos, es posible observar incrementos del ca195 sérico (19,6%), principalmente de origen digestivo (25,3%); c) la presencia de ictericia estuvo asociada con elevaciones séricas del antígeno; d) en los carcinomas coloréateles, las concentraciones y porcentajes de positividades del ca195 se correlacionaron significativamente con el estadio clínico, y la dosificación conjunta de sea y ca195 (mayor 12 u/ml) obtuvo una sensibilidad global del 74,8%, significativamente más elevada (p<0,001), que la obtenida con cada uno por separado (61,8% vs 63,5%, respectivamente); e) las concentraciones séricas y el porcentaje de positividades del ca195 sérico fueron superiores estadísticamente (p<0,05) en los tumores cólicos que en los rectales. En ambas localizaciones, una cifra antigénica de 19 u/ml fue, mediante análisis multivariante, un factor pronostico independiente de peor supervivencia, situándose tras el estadio tumoral [...

Joint Tumor Bud–MMP/TIMP Count at the Invasive Front Improves the Prognostic Evaluation of Invasive Breast Carcinoma

Background: Tumor budding is a histological phenomenon consisting of the formation of small clusters of one to five undifferentiated malignant cells detached from the main tumor mass which are observed in the tumor stroma. In the present study, we investigated the prognostic significance of tumor budding in breast cancer and its relationship with the expressions of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs). Methods: The number of buds was counted in whole-tissue sections from 153 patients with invasive ductal carcinomas who underwent a long follow-up period. In addition, an immunohistochemical study of MMP-9, -11, and -14 TIMP-1 and -2 expression by cell types at the invasive tumor front was carried out. Results: There was a wide variability in the number of buds among tumors, ranging from 0 to 28 (median = 5). Tumor budding count ≥ 4 was the optimal cut-off to predict both relapse-free and overall survival. High-grade tumor budding was associated with MMP/TIMP expression by cancer-associated fibroblasts. In addition, we found that the combination of tumor budding grade with MMP/TIMP expression by stromal cells, and especially with MMP-11 expression by mononuclear inflammatory cells, significantly improved the prognostic evaluation. Conclusion: High-grade tumor budding is associated with a more aggressive tumor phenotype, which, combined with MMP/TIMP expression by stromal cells at the invasive front of the tumor, identifies patients with poor prognosis.</jats:p

Prognostic Influence of Tumor Stroma on Breast Cancer Subtypes

Aims: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of MMPs and TIMPs on prognosis in different breast cancer subtypes. Materials and Methods: 247 tumors of patients with primary ductal invasive breast cancer were categorized into one of four major subtypes, using the three standard immunohistochemical markers (ER, PR and HER/Neu 2 receptor status). An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)-9, -11 and -14, and tissue inhibitors of metalloproteinase (TIMP)-1 and –2. Results: MMP-11 expression by MICs was significantly and strongly associated with prognosis in all breast cancer subtypes. There were other significant associations with poor prognosis in Luminal A tumors: expressions of MMP-9, -11, and TIMP-2 by CAFs, in Luminal B tumors: MMP-14 expression by MICs and TIMP-2 expression by MICs, in HER-2-positive tumors: expression of MMP-9 by MICs and in triple-negative breast cancers (TNBC): expression of TIMP-1 by MICs. Conclusion: Characterization of both tumor stromal CAFs and MICs, with regard to the expression of MMPs and TIMPs, improve the prognostic evaluation of all breast cancer subtypes