RESUMEN
Primary hepatic neuroendocrine carcinoma is an extremely rare liver tumor. We herein report a case of primary hepatic neuroendocrine carcinoma coexisting with a hemangioma in a 66-year-old man. Ultrasonography, computed tomography, and magnetic resonance imaging showed a tumor (1.5 cm in diameter) coexisting with a hemangioma in the lateral segment of the liver. Liver biopsy showed malignant cells, and several examinations revealed no alternative primary source. We performed a lateral segmentectomy. Microscopically, the tumor cells had round to oval nuclei and eosinophilic cytoplasm, proliferated in thick trabeculae or solid nests, and formed a focal rosette pattern. Mitotic cells were frequently observed. Immunohistochemically, the tumor cells were positive for the endocrine markers chromogranin A, neuron-specific enolase, and neural cell adhesion molecule, but negative for alpha-fetoprotein and hepatocyte-specific antigen. The patient is still alive after 3 months, without recurrence.
Asunto(s)
Carcinoma Neuroendocrino/patología , Hemangioma/patología , Neoplasias Hepáticas/patología , Neoplasias Primarias Secundarias/patología , Carcinoma Neuroendocrino/diagnóstico por imagen , Diagnóstico Diferencial , Hemangioma/diagnóstico por imagen , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/diagnóstico por imagen , Radiografía , Resultado del TratamientoRESUMEN
BACKGROUND: Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated. METHODS: The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously. RESULTS: The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS. CONCLUSION: The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.
Asunto(s)
Neoplasias de la Mama/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica , Antígeno Ki-67/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática/patología , Persona de Mediana Edad , Receptor ErbB-2/metabolismoRESUMEN
Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.
Asunto(s)
Angiopoyetina 2/biosíntesis , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Microcirculación , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: It was previously demonstrated that PTEN protein expression is reduced in 67 of 236 (28%) breast carcinomas. Recent experimental studies suggested that the cell cycle inhibitor p27Kip1 (p27) is a downstream mediator through which PTEN negatively regulates cell cycle progression. METHODS: The immunohistochemic expression of p27 and PTEN protein expression was evaluated in a series of 228 invasive ductal carcinomas of the breast. RESULTS: PTEN protein expression was found to have decreased in 65 of 228 (29%) cases, while the nuclear accumulation of p27 protein was low in 99 of 228 (43%) cases. A reduced PTEN protein expression correlated significantly (P = 0.0214) with a low p27 protein expression. Univariate analysis indicated that the patients demonstrating a combined decrease in PTEN and p27 protein expression have a significantly (P = 0.0044) worse disease-free survival (DFS) than those with other combinations of these two protein expression patterns, while multivariate analysis indicated that the lymph node status, MIB-1 counts, and the combination of PTEN/p27 protein expression (P = 0.0452) are independently significant prognostic factors for DFS. CONCLUSIONS: A reduced PTEN protein expression correlated significantly with a low p27 protein expression in breast carcinoma. The finding that the patients with a combined decrease in both protein expressions had a poor prognosis thus suggests that a combined loss of PTEN and p27 function is associated with an aggressive phenotype in breast carcinoma.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Ductal/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/biosíntesis , Fosfohidrolasa PTEN/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal/mortalidad , Carcinoma Ductal/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , PronósticoRESUMEN
Stromal cells, within and around the tumor, as well as tumor cells are both involved in angiogenesis which is an important step in tumor growth and metastasis. Among such stromal cells, macrophages are known to play various roles in tumor angiogenesis and have thus been called tumor-associated macrophages (TAMs). The TAM density, vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) were immunohistochemically evaluated in 249 paraffin-embedded sections of invasive ductal carcinoma of the breast. The TAM density and MVD were assessed as the average density of three hot spots at a magnification of x400 and x200, respectively. The TAM density showed a significant correlation with both the VEGF expression and MVD, while a significant correlation was also found between the VEGF expression and MVD. The TAM density was also associated with the nuclear grade, estrogen receptor status and MIB-1 count. Patients with a high TAM density had a significantly (p=0.0025) worse disease-free survival (DFS) prognosis than those with a low TAM density, while univariate analyses also indicated both the MVD (p<0.0001) and VEGF expression (p=0.0152) to be prognostic factors for DFS. A multivariate analysis indicated MVD (p=0.0057), as well as lymph node metastasis and the MIB-1 count, to be independently significant prognostic factors for DFS. In conclusion, the present study demonstrated a close association between TAM infiltration and both the VEGF expression and MVD. The prognostic significance of MVD was the strongest among these three factors in breast cancer. These findings suggested that the prognostic implications of TAM infiltration are due to the involvement of TAMs in tumor angiogenesis.
Asunto(s)
Neoplasias de la Mama/patología , Macrófagos/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Neovascularización Patológica/patología , Pronóstico , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
OBJECTIVE: The PTEN tumor suppressor gene has been demonstrated to be inactivated in a variety of human tumors. In breast cancer, the PTEN gene mutation is not commonly found whereas loss of heterozygosity affecting the PTEN locus is frequently found. The aim of this study was to analyze PTEN protein expression in breast cancer and to evaluate the prognostic significance of PTEN protein expression. METHODS: Paraffin-embedded sections ofinvasive ductal carcinoma of the breast were immunohistochemically stained for PTEN protein expression in 236 breast cancers. The immunohistochemical expression of breast cancer cells was judged to be either normal or reduced compared with the PTEN protein expression of the normal mammary gland. RESULTS: The expression of PTEN protein was found to have decreased in 67 (28%) of 236 breast cancers. The reduced expression correlated with lymph node metastasis (p = 0.0371), but not with tumor size, nuclear grade, MIB-1 counts or p53 protein expression. Univariate analysis indicated that patients with a reduced PTEN expression had a shorter disease-free survival (DFS) than those with a normal PTEN expression (p = 0.0174). Univariate analyses also determined tumor size, lymph node metastases, nuclear grade, MIB-1 counts, p53 protein as well as PTEN protein expression to be significant factors for DFS, while multivariate analysis determined lymph node metastases and the MIB-1 counts to be independent significant factors for DFS. CONCLUSIONS: The inactivation of PTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers. The reduced expression of PTEN protein correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Metástasis Linfática , Invasividad Neoplásica/patología , Monoéster Fosfórico Hidrolasas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfohidrolasa PTEN , Pronóstico , Receptores de Estrógenos/metabolismo , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: A close correlation of the p53 protein expression to nuclear pleomorphism and proliferative activity in breast cancer has been reported. The prognostic implications of p53 protein expression, however, in relation to nuclear pleomorphism and proliferative activity in breast cancer remain controversial. PATIENTS AND METHODS: Nuclear pleomorphism and immunohistochemical reactivity for p53 protein and MIB-1 were evaluated on formalin-fixed paraffin-stored sections from 250 patients with breast cancer for whom the median follow-up duration was 6.4 years. RESULTS: p53 protein expression was positive in 66 (26.4%) of 250 cases. Nuclear pleomorphism was grade I or II in 169 (67.6%) cases and grade III in 81(32.4%)cases. The MIB-1 counts were more than 10% in 102 (40.8%) cases and less than 10% in 148 (59.2%) cases. There was a close correlation between p53 protein expression and nuclear pleomorphism (p<0.0001) and between p53 protein expression and MIB-1 counts (p<0.0001). Univariate analyses showed the 66 cases with positive p53 protein expression to have a significantly (p=0.0284) worse disease free survival (DFS) than the 184 cases with negative p53 protein expression. A multivariate analysis, however, on the variables including all of p53 protein expression, nuclear pleomorphism and MIB-1 counts indicated the MIB-1 counts (p=0.0041) as well as the lymph node status to be independently significant factors for DFS, while neither p53 protein expression nor nuclear pleomorphism were independently significant factors for DFS. CONCLUSION: The present study demonstrated that the p53 protein expression, nuclear pleomorphism and MIB-1 counts all demonstrated prognostic significance for breast cancer, while the most significant prognostic indicator among these three biological parameters was the MIB-1 counts.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Núcleo Celular , Perfilación de la Expresión Génica , Antígeno Ki-67/análisis , Proteína p53 Supresora de Tumor/biosíntesis , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Although the prognostic value of microvessel density (MVD) has been studied in breast cancer, the results still remain controversial. PATIENTS AND METHODS: Paraffin embedded sections of invasive ductal carcinoma of the breast were immunohistochemically stained for factor VIII- related antigen in 252 patients with a median follow-up duration of 7.0 years. MVD quantification of the three most vascular areas at a magnification of x 200 was performed. RESULTS: The 252 patients were stratified into high and low MVD groups according to a cut-off value that was the upper one-third MVD value of all patients. The patients with a high MVD had a significantly worse outcome in terms of both disease free survival (DFS) (p< 0.0001) and overall survival (OS) (p= 0.0012) compared with those with a low MVD. The same effects were seen in patients with lymph node negative as well as positive breast cancer. Multivariate analyses indicated the nodal status, nuclear grade and MVD (p= 0.0001) to be independent prognostic factors for the DFS, while the nodal status, estrogen receptor status, tumor size and MVD (p= 0.0006) were independent prognostic factors for the OS. CONCLUSION: MVD was found to be an independent prognostic indicator of recurrence and death for breast cancer, and is therefore considered to be a useful factor for selecting high risk patients to receive adjuvant therapies.