Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado / No disponible

Introducción: El carcinoma colorrectal (CCR) puede inducir una respuesta inmunitaria antitumoral mediada por linfocitos T, que expresan el CD3.ObjetivosAnalizar el valor pronóstico de la expresión tisular de CD3 intraepitelial (CD3I) globalmente y en los estadios tumorales menos avanzados. Métodos Revisamos 251 CCR resecados, con evolución controlada, estudiando inmunohistoquímicamente la expresión de CD3I. Determinamos mediante análisis multivariante las variables con valor pronóstico independiente sobre la supervivencia del CCR. Analizamos la expresión de CD3I (+), en relación con la supervivencia y la progresión tumoral, globalmente y en los pacientes en estadio pTNM (I-II), estableciendo su sensibilidad, especificidad, valor predictivo positivo (VP+) y negativo y precisión diagnóstica. Resultados Un 25,9% de los CCR fueron CD3I (+). Tras un seguimiento medio de 74 meses, la expresión CD3I (+) mostró un valor pronóstico favorable para la supervivencia en el análisis multivariante (p=0,045). Las curvas de supervivencia y no progresión tumoral resultaron más favorables en los casos CD3I (+), tanto globalmente (p=0,009 y p=0,004, respectivamente), como en estadio I-II (p=0,029 y p=0,015). La especificidad (E) y valor predictivo positivo (VP+) de la expresión de CD3I (+) fueron: supervivencia global, E=0,89; VP+=0,91. Estadio (I-II): E=0,94; VP+=0,98. Sin progresión tumoral global: E=0,89; VP+=0,88. Estadio (I-II): E=0,92; VP+=0,96.ConclusionesLa expresión de CD3I conlleva un valor pronóstico favorable independiente, con porcentajes significativamente superiores de supervivencia y de no progresión tumoral, manteniéndose este mejor pronóstico en los estadios menos avanzados (I-II) y presentando unas elevadas tasas de especificidad y valor predictivo positivo (AU)

Introduction: Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3.Objectives: To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages. Methods: We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy ofCD3I expression were analyzed. Results: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p = 0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p = 0.009 and p = 0.004, respectively), and in stages I-II(p = 0.029 and p = 0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94;positive predictive value =0.98. Absence of tumoral progression: overall: specificity = 0.89;positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96.Conclusions: CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value (AU)

Manifestación inicial de leucemia linfoblástica aguda en la mama. Descripción de un caso y revisión de la bibliografía / Initial manifestation of acute lymphoblastic leukemia in the breast. Description of a case and a literature review

Presentamos un caso de leucemia linfoblástica aguda (LLA) de células precursoras B en una mujer de 19 años que inició en forma de nódulo único en la mama derecha. La paciente recibió tratamiento con quimioterapia y, posteriormente, transplante HLA (del inglés Human Leukocyte Antigens) idéntico de donante no emparentado. Dos años después de iniciarse la enfermedad, tuvo una recaída y presentó múltiples nódulos bilaterales en las mamas. Hasta la fecha, sólo se han publicado 33 casos de LLA en mama, y sólo 11 de ellos, incluido el nuestro, con afectación mamaria como manifestación inicial de la leucemia. Es importante tener en cuenta la LLA en casos de mujeres jóvenes con lesiones bilaterales y múltiples en mama, ya que los estudios radiológicos son inespecíficos. Estas pacientes, además de un estudio histológico, podrían beneficiarse de un estudio de sangre periférica de inicio con el fin de acelerar el proceso diagnóstico (AU)

We present a case of acute lymphoblastic leukaemia (ALL) in a 19-year female who presented with solitary mass in the right breast as an initial presentation of the disease. The patient received chemotherapy treatment with the PETHEMA LAL-high risk 2003 protocol, and later an HLA-identical bone marrow transplantation was performed. Two years after onset of the disease she had a recurrence, having multiple nodes in both breasts. She then had an HLA-identical bone marrow transplantation from was performed. Two years later, she showed recurrence of ALL in both breasts. To the best of our knowledge, only 33 cases have been reported in the literature, and in only 11 of them, including our, the infiltration of the breast was the initial presentation of the disease. A high level of suspicion is important in those cases of young women with bilateral and multiple masses, because unfortunately there is no reliable imaging pattern suggestive of leukemic infiltration of the breast. In addition to a histological study, a complete blood count should be performed at start up to speed up the diagnosis (AU)

[Predictive value of intraepithelial (CD3) T-lymphocyte infiltration in resected colorectal cancer]. / Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado.

INTRODUCTION: Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3. OBJECTIVES: To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages. METHODS: We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed. RESULTS: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p=0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p=0.009 and p=0.004, respectively), and in stages I-II (p=0.029 and p=0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity=0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96. CONCLUSIONS: CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value.

Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer.

AIM: to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. PATIENTS AND METHODS: three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which presented significant differences in multivariate logistic regression, dividing patients into three groups. RESULTS: variables with prognostic value for metachronicity were distal cancer location: OR = 2.30 (1.03-5.13), alcohol intake: OR = 2.20 (1.08-4.48), presence of synchronous adenomas: isolated: OR = 2.47 (1.03-4.48), multiple: OR = 4.26 (1.78-10.17), and presence of synchronous advanced adenoma: OR = 2.91 (1.52-12.60). Tumor MUC-5 expression proved to have a protective role: OR = 0.23 (0.08-0.66). An individual risk score was established considering these variables and patients could be classified into three groups, with a discrimination power for metachronicity of p < 0.0000001. Classification in high and low risk groups had a sensitivity = 75.32%, specificity = 84.21%, positive predictive value = 75.34%, negative predictive value = 92.31% and global diagnostic accuracy = 80.75%. CONCLUSIONS: the identification of risk factors for the development of metachronous lesions allow to calculate, at the time of surgical treatment, an individual prognostic index and to classify patients into three different risk groups. In high and low risk groups, both specificity and accuracy were acceptable for the prognosis of metachronous lesions, being remarkable the negative predictive power of our classification, which could become relevant when planning a different endoscopic follow up of these patients.

Elaboración de un índice individual del riesgo para el desarrollo de lesiones neoplásicas metacrónicas en el cáncer colorrectal resecado / Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer

Objetivo: identificar posibles factores de riesgo para desarrollar lesiones metacrónicas en el cáncer colorrectal, elaborando un índice pronóstico individual del riesgo. Material y métodos: revisamos 382 cánceres colorrectales resecados. Comparamos la diferente incidencia de lesiones metacrónicas en 40 variables referentes al paciente y a las lesiones neoplásicas iniciales. Con aquellas que mostraron diferencias significativas en el análisis estadístico multivariable, elaboramos un índice individual de riesgo, clasificando los pacientes en 3 grupos de riesgo de metacronicidad. Resultados: las variables con valor pronóstico para la metacronicidad fueron: localización distal del cáncer: OR = 2,30 IC 95% (1,03-5,13); consumo de alcohol: OR = 2,20 IC 95% (1,08-4,48); presencia de adenoma sincrónico único: OR = 2,47 IC 95% (1,03- 4,48) o múltiple: OR = 4,26 IC 95% (1,78-10-17) y adenoma avanzado: OR = 2,91 IC 95% (1,52-12,60). La expresión tisular de MUC-5 en el tumor mostró valor protector: OR = 0,23 IC 95% (0,08-0,66). Con estas variables se elaboró un índice pronóstico para el desarrollo de lesiones metacrónicas, clasificando a los individuos en tres grupos de riesgo, con un poder de discriminación de p < 0,000001. El índice mostró una sensibilidad de 75,32%, especificidad = 84,21%, valor predictivo positivo = 75,34%, negativo = 92,31%, con una precisión diagnóstica = 80,75%. Conclusiones: la identificación de variables de riesgo para desarrollar lesiones metacrónicas permitió calcular, desde la cirugía, un índice pronóstico individual, clasificando los pacientes en 3 grupos de riesgo. Los grupos de alto y bajo riesgo registraron una aceptable especificidad y precisión para el pronóstico de lesiones metacrónicas, destacando el elevado poder predictivo negativo de nuestra clasificación, que aconsejaría un diferente seguimiento endoscópico(AU)

Aim: to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. Patients and methods: three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which presented significant differences in multivariate logistic regression, dividing patients into three groups. Results: variables with prognostic value for metachronicity were distal cancer location: OR= 2.30 (1.03-5.13), alcohol intake: OR = 2.20 (1.08-4.48), presence of synchronous adenomas: isolated: OR = 2.47 (1.03-4.48), multiple: OR = 4.26 (1.78-10.17), and presence of synchronous advanced adenoma: OR= 2.91 (1.52- 12.60). Tumor MUC-5 expression proved to have a protective role: OR = 0.23 (0.08-0.66). An individual risk score was established considering these variables and patients could be classified into three groups, with a discrimination power for metachronicity of p < 0.0000001. Classification in high and low risk groups had a sensitivity = 75.32%, specificity = 84.21%, positive predictive value = 75.34%, negative predictive value = 92.31% and global diagnostic accuracy = 80.75%. Conclusions: the identification of risk factors for the development of metachronous lesions allow to calculate, at the time of surgical treatment, an individual prognostic index and to classify patients into three different risk groups. In high and low risk groups, both specificity and accuracy were acceptable for the prognosis of metachronous lesions, being remarkable the negative predictive power of our classification, which could become relevant when planning a different endoscopic follow up of these patients(AU)

Descripción de cuatro casos de histoplasmosis importada en Navarra / Imported histoplasmosis in Navarra: presentation of four cases

Objetivo. La histoplasmosis es una infección fúngica causada por el hongo dimórfico Histoplasma capsulatum. En los últimos años, su incidencia en Espa¿na ha aumentado debido, principalmente, a la mayor presencia de población inmigrante procedente de América y al incremento de viajes a dicho continente por turismo o cooperación. Nuestro objetivo ha sido revisar las características clínicas de los casos de histoplasmosis diagnosticados en nuestro centro en los últimos 6 años. Casos clínicos. Se diagnosticaron 4 casos pertenecientes a 4 pacientes de origen sudamericano, 3 de los cuales eran VIH positivos y 1 diagnosticado de dermatomiositis y en tratamiento con fármacos inmunosupresores. El diagnóstico de laboratorio se llevó a cabo mediante estudio anatomopatológico y microbiológico, mediante cultivo y PCR específica directa de la muestra. Discusión. Al tratarse de una infección importada es necesario tener un alto índice de sospecha y realizar una anamnesis detallada, para llegar a su diagnóstico. Es una infección a tener en cuenta en el diagnóstico diferencial del síndrome febril en pacientes inmunodeprimidos, tanto VIH positivos como en tratamiento inmunosupresor, que sean originarios de zonas endémicas o que tengan antecedentes de estancia en ellas(AU)

Objetive. Histoplasmosis is a fungal infection caused by the dimorphic fungi Histoplasma capsulatum. Its incidence in Spain has increased in recent years, mainly due to the increased presence of immigrants from Latin America and increased travel to the continent for tourism and cooperation. Our aim was to review the clinical characteristics of cases of histoplasmosis diagnosed in our hospital during the last six years. Case Reports. We diagnosed 4 cases from 4 patients from South America, 3 ofwhomwere HIV positive and 1 diagnosed with dermatomyositis was treated with immunosuppressive drugs. The laboratory diagnosis was carried out by histological and microbiological study, by culture and specific PCR directly on the sample. Discussion. As it is an imported infection there needs to be a high level of suspicion and a detailed history taken to get a diagnosis. This infection requires a differential diagnosis between febrile syndrome in immunosuppressed patients, both HIV positive and immunosuppressive therapy, which originate from endemic areas, or who have a history of staying in them(AU)

[Imported histoplasmosis in Navarra: presentation of four cases]. / Descripción de cuatro casos de histoplasmosis importada en Navarra.

OBJECTIVE: Histoplasmosis is a fungal infection caused by the dimorphic fungi Histoplasma capsulatum. Its incidence in Spain has increased in recent years, mainly due to the increased presence of immigrants from Latin America and increased travel to the continent for tourism and cooperation. Our aim was to review the clinical characteristics of cases of histoplasmosis diagnosed in our hospital during the last six years. CASE REPORTS: We diagnosed 4 cases from 4 patients from South America, 3 of whom were HIV positive and 1 diagnosed with dermatomyositis was treated with immunosuppressive drugs. The laboratory diagnosis was carried out by histological and microbiological study, by culture and specific PCR directly on the sample. DISCUSSION: As it is an imported infection there needs to be a high level of suspicion and a detailed history taken to get a diagnosis. This infection requires a differential diagnosis between febrile syndrome in immunosuppressed patients, both HIV positive and immunosuppressive therapy, which originate from endemic areas, or who have a history of staying in them.

¿Presentan un desplazamiento hacia segmentos más proximales los adenomas metacrónicos en el cáncer colorrectal? / Do metachronous colorectal adenomas show proximal shift?

ObjetivoEstudiar en el cáncer colorrectal (CCR) la posibilidad de un desplazamiento hacia segmentos más proximales de los adenomas metacrónicos tras la extirpación del tumor y sus lesiones sincrónicas.Material y métodosRevisamos 382 CCR resecados, diagnosticados y controlados evolutivamente mediante colonoscopias completas. Comparamos la localización de los adenomas metacrónicos con respecto a los sincrónicos globalmente y según el sexo, el tamaño y el número de las lesiones sincrónicas. Analizamos la frecuencia de localización exclusivamente proximal en los adenomas metacrónicos de primera, segunda y tercera generación y la comparamos con la de los adenomas sincrónicos.ResultadosUn 54,5% de los pacientes con CCR presentó adenomas sincrónicos. Tras una mediana de seguimiento de 48 meses, con 2,74±1,47 colonoscopias/caso, el 42,4% desarrolló adenomas metacrónicos, el 16,8% desarrolló adenomas de segunda generación y el 7,3% desarrolló adenomas de tercera generación. Registramos un desplazamiento proximal de los adenomas metacrónicos en ambos sexos, independientemente del tamaño y del número de las lesiones iniciales. La frecuencia de localización exclusivamente proximal de los adenomas fue sincrónico=21,2%; primera generación de metacrónicos=39,5% (p=0,0001; OR=2,46 [1,50–3,95]); segunda generación=42,6% (p=0,0008; OR=2,77 [1,44–5,31]) y tercera generación=39,3% (p=0,0003; OR=2,41 [0,97–5,93]).ConclusionesRegistramos una elevada incidencia de adenomas sincrónicos y metacrónicos. Observamos un «giro proximal» de los adenomas metacrónicos, independientemente del sexo y del tamaño y el número de las lesiones sincrónicas. Esta tendencia se mantiene en las sucesivas generaciones de adenomas metacrónicos, lo que obliga a efectuar colonoscopias completas durante todo el seguimiento postoperatorio(AU)

ObjectiveTo study the possibility of shift toward more proximal sites in colorectal cancer (CRC) after resection of tumors and synchronous lesions.Material and methodsWe reviewed 382 resected CRC diagnosed and followed-up with complete colonoscopies. The localization of metachronous adenomas was compared with that of synchronous lesions overall and by sex, tumoral size and the number of synchronous lesions. The frequency of exclusively proximal localization in first-, second- and third-generation metachronous adenomas was compared with that of synchronous adenomas.ResultsA total of 54.5% of patients with CRC had synchronous adenomas. After a median follow-up of 48 months, with 2.74±1.47 colonoscopies/case, 42.4% developed metachronous adenomas, 16.8% second-generation adenomas and 7.3% third-generation lesions. Proximal shift was found in metachronous adenomas in both sexes, independently of tumoral size and the number of initial lesions. The frequency of exclusively proximal localization in adenomas was 21.2% in synchronous lesions, 39.5% in first-generation metachronous adenomas (p=0.0001; OR=2.46 [1.50–3.95]), 42.6% in second-generation metachronous adenomas (p=0.0008; OR=2.77 [1.44–5.31]) and 39.3% in third-generation metachronous lesions (p=0.0003; OR=2.41 [0.97–5.93]).ConclusionsWe found a high incidence of synchronous and metachronous adenomas. Metachronous adenomas showed a proximal shift, independently of sex, tumoral size and the number of synchronous lesions. This tendency was maintained in successive generations of metachronous adenomas, thus demonstrating the need to perform complete colonoscopies throughout the postoperative follow-up period(AU)

[Do metachronous colorectal adenomas show proximal shift?]. / ¿Presentan un desplazamiento hacia segmentos más proximales los adenomas metacrónicos en el cáncer colorrectal?

OBJECTIVE: To study the possibility of shift toward more proximal sites in colorectal cancer (CRC) after resection of tumors and synchronous lesions. MATERIAL AND METHODS: We reviewed 382 resected CRC diagnosed and followed-up with complete colonoscopies. The localization of metachronous adenomas was compared with that of synchronous lesions overall and by sex, tumoral size and the number of synchronous lesions. The frequency of exclusively proximal localization in first-, second- and third-generation metachronous adenomas was compared with that of synchronous adenomas. RESULTS: A total of 54.5% of patients with CRC had synchronous adenomas. After a median follow-up of 48 months, with 2.74+/-1.47 colonoscopies/case, 42.4% developed metachronous adenomas, 16.8% second-generation adenomas and 7.3% third-generation lesions. Proximal shift was found in metachronous adenomas in both sexes, independently of tumoral size and the number of initial lesions. The frequency of exclusively proximal localization in adenomas was 21.2% in synchronous lesions, 39.5% in first-generation metachronous adenomas (p=0.0001; OR=2.46 [1.50-3.95]), 42.6% in second-generation metachronous adenomas (p=0.0008; OR=2.77 [1.44-5.31]) and 39.3% in third-generation metachronous lesions (p=0.0003; OR=2.41 [0.97-5.93]). CONCLUSIONS: We found a high incidence of synchronous and metachronous adenomas. Metachronous adenomas showed a proximal shift, independently of sex, tumoral size and the number of synchronous lesions. This tendency was maintained in successive generations of metachronous adenomas, thus demonstrating the need to perform complete colonoscopies throughout the postoperative follow-up period.

[Primary adenocarcinoma of the seminal vesicles]. / Adenocarcinoma primario de vesículas seminales.

OBJECTIVES: To report one case of primary adenocarcinoma of the seminal vesicles. METHODS/RESULTS: We report the case of a 69-year-old man with obstructive voiding symptoms. Digital rectal examination reveals a marked enlargement of posterior area of the prostate and surrounding tissues. Transrectal needle biopsy shows a primary adenocarcinoma of the seminal vesicles. CONCLUSION: Primary adenocarcinoma of the seminal vesicles is an extremely uncommon neoplasm that is often difficult to diagnose as it has in specific morphology and can be confused with other primary adenocarcinomas from prostate, bladder or colon.

Adenocarcinoma primario de vesículas seminales / Primary adenocarcinoma of the seminal vesicles

OBJETIVOS: Presentar un caso de adenocarcinoma primario de vesícula seminal.MÉTODO/RESULTADOS: Varón de 69 años con síntomas de uropatía obstructiva, que presenta al tacto rectal un agrandamiento del área posterior de la próstata y tejidos adyacentes. La biopsia transrectal revela un adenocarcinoma papilar primario de vesículas seminales.CONCLUSIÓN: El adenocarcinoma primario de vesículas seminales es una neoplasia extremadamente infrecuente, que es de difícil diagnóstico tanto por su morfología inespecífica como por su localización, dado que se puede confundir con otros adenocarcinomas primarios como de la próstata, vejiga o recto(AU)

OBJECTIVES:To report one case of primary adenocarcinoma of the seminal vesicles.METHODS/ RESULTS: We report the case of a 69-year-old man with obstructive voiding symptoms. Digital rectal examination reveals a marked enlargement of posterior area of the prostate and surrounding tissues. Transrectal needle biopsy shows a primary adenocarcinoma of the seminal vesicles.CONCLUSION: Primary adenocarcinoma of the seminal vesicles is an extremely uncommon neoplasm that is often difficult to diagnose as it has inespecific morphology and can be confused with other primary adenocarcinomas from prostate, bladder or colon(AU)

Large cell carcinoma of the lung: an endangered species?

This study aims to evaluate large cell carcinomas (LCC) of the lung with a panel of immunohistochemical markers in an attempt to identify tumors belonging to other categories. We analyzed a tissue microarray platform of 101 LCC with a panel of 31 monoclonal antibodies. The tumors were 82 (81.3%) classic LCC, 7 (6.9%) neuroendocrine LCC, 6 (5.9%) lymphoepithelioma-like LCC, 3 (2.9%) basaloid LCC, 2 (2%) clear cell LCC, and 1 (1%) LCC with rhabdoid phenotype. Characteristic classic LCC immunophenotype was loss of staining with CK5/6, CK14 positive in most squamous cell carcinoma (SCC), lack of MOC 31 positive in most adenocarcinomas, and positive immunoreactivity to EGFR, PDGFR-alpha and c-kit. 27 of 82 classic LCC (32.9%) were re-classified as adenocarcinomas, because they coexpressed TTF-1, CK7, and CK19, and were negative for p63. 31 (37.8%) of 82 classic LCC were reclassified as poorly differentiated SCC, based on their immunoreactivity with 34betaE12, p63, thrombomodulin, and CD44v6. 16 (19.5%) of 82 classic LCC correspond to undifferentiated adenosquamous carcinomas, since they displayed conflicting immunostaining for markers of both SCC and adenocarcinomas. The use of 7 immunohistochemical markers, consisting of TTF-1, CK7, CK19, p63, 34betaE12, thrombomodulin, and CD44v6, markedly reduces dramatically to less than 10%, the number of classic LCC by readily identifying cases of poorly differentiated SCCs, adenosquamous carcinoma and adenocarcinomas.

Differences and molecular immunohistochemical parameters in the subtypes of infiltrating ductal breast cancer.

Breast cancer is a heterogeneous disease, and patients are categorized into subtypes according to gene expression. We studied the associations among molecular, immunohistochemical, and clinicopathologic features and their distribution according to the subtypes luminal, HER2, basal, and normal-like in 60 patients with invasive ductal breast carcinoma without distant metastasis at the time of diagnosis (M0). We evaluated the hypermethylation of the CDH-1, RASSF1A, SIAH-1 and TSLC-1 genes by methylation-specific polymerase chain reaction and the expression of p53, bcl-2, cyclin D1, E-cadherin, and beta-catenin proteins in tissue microarrays by immunohistochemical analysis. Expression of bcl-2 was associated with the luminal subtype (P=.003), and CDH-1 hypermethylation was present preferentially in HER2 tumors (P=.038). The basal subtype was characterized by the expression of beta-catenin (P=.003). The hypermethylation of CDH-1 and the expression of bcl-2, cyclin D1, and beta-catenin proteins differ among breast cancer subtypes.

Hypermethylation, risk factors, clinical characteristics, and survival in 235 patients with laryngeal and hypopharyngeal cancers.

BACKGROUND: It has been established that promoter hypermethylation occurs in several genes during the pathogenesis of head and neck cancer. The authors investigated the role played by the hypermethylation of 4 cancer-related genes in the survival of patients who had laryngeal and hypopharyngeal cancer and in the occurrence of second primary tumors. METHODS: Archival paraffin-embedded tissue (PET) samples were available from patients who were enrolled in a multicentric European case-control study that was performed between 1979 and 1982 and was followed up to 2000. Genomic DNA extracted from 235 PET samples were analyzed for promoter methylation status of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase (DAP-K), and E-cadherin genes by using a methylation-specific polymerase chain reaction assay. RESULTS: Hypermethylation was present in 44% of samples for p16, in 27% of samples for MGMT, in 42% of samples for DAP-K, and in 43% of samples for E-cadherin. Hypermethylation of either individual genes or their combination was not associated with mortality from all causes, mortality from upper aerodigestive tract cancer, or the occurrence of second primary tumors. CONCLUSIONS: The analysis of a large series of patients with laryngeal and hypopharyngeal cancer suggested that hypermethylation is a frequent event in laryngeal and hypopharyngeal cancer, but it is not a predictor of mortality or second primary cancer.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype.

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).

[Association between microsatellite instability and clinico-pathological characteristics in sporadic colon cancer]. / Asociación entre la inestabilidad de microsatélites y las características clínicas y anatomopatológicas en pacientes con cáncer de colon esporádico.

BACKGROUND AND OBJECTIVE: Currently, colon cancer is a leading cause of cancer death world-wide. It progresses according to three molecular pathways, named suppressor, mutador and methylator. Microsatellite instability is a hallmark of the lack of reparation, of DNA mismatches and it characterizes a subset of colon tumors (unstable tumors, MSI). MSI-H patients (high degree of microsatellite instability) seem to share clinico-pathological differences with MSS (microsatellite stable) and MSI-L (low degree of microsatellite instability) patients. In this study, associations between high degree of microsatellite instability and pathological (location, mucinous content, differentiation grade, stages T3N0, stages II and III) and clinical features (response to chemotherapy, disease-free survival and overall survival) were evaluated. PATIENTS AND METHOD: 117 patients with sporadic colon cancer were classified into two populations (MSS/MSI-L and MSI-H) by using PCR and electrophoresis of seven microsatellites, according to the National Cancer Institute recommendations. RESULTS: MSI-H tumors tended to be located in the right colon (p = 0.022) and were of mucinous histologic type (p = 0.04). No differences in disease-free survival and overall survival between group of stage II and III patients with MSS/ MSI-L and corresponding ones with MSI-H colon cancer were found (p = 0.54, p = 0.37, respectively). Conversely, MSI-H patients with stage II colon cancer had a favourable prognosis (p = 0.027). Nevertheless, response to 5-fluorouracil (5-FU) and leucovorin was similar in MSS/ MSI-L and MSI-H groups (p = 0.38). CONCLUSIONS: MSI-H patients are characterized by certain pathological features; those MSI-H patients with a stage II seem to have a better prognosis than MSS/ MSI-L patients.

Asociación entre la inestabilidad de microsatélites y las características clínicas y anatomopatológicas en pacientes con cáncer de colon esporádico / Association between microsatellite instability and clinico-pathological characteristics in sporadic colon cancer

FUNDAMENTO Y OBJETIVO: La inestabilidad de microsatélites derivada del fallo en la reparación delos falsos emparejamientos del ADN es la alteración característica de los tumores de la vía mutadorao inestables (MSI). Tales casos parecen presentar diferencias desde el punto de vista clinicopatológicocon los tumores de la vía supresora o estables (MSS). Los tumores con alto gradode inestabilidad (MSI-H) parecen constituir una nueva entidad de tumores con diferencias endeterminadas características anatomopatológicas y clínicas con respecto a los tumores estables(MSS) e inestables de bajo grado (MSI-L). En el presente estudio se valora la posible asociaciónentre el alto grado de inestabilidad de microsatélites con la localización, contenido mucinoso,grado de diferenciación, estadio, así como el intervalo libre de enfermedad y supervivencia.PACIENTES Y MÉTODO: Se clasifica a 117 pacientes con cáncer de colon esporádico en las poblacionesMSS/MSI-L y MSI-H (siguiendo las recomendaciones del National Cancer Institute) mediantereacción en cadena de la polimerasa y electroforesis de 7 microsatélites.RESULTADOS: Los tumores MSI-H tendieron a localizarse en el colon derecho (p = 0,022) y a presentarcontenido mucinoso (p = 0,04). El conjunto de pacientes MSI-H de estadios II y III no presentóintervalos libres de enfermedad ni períodos de supervivencia más prolongados (p = 0,54, p= 0,37, respectivamente). Los tumores MSI-H de estadio II presentaron períodos de supervivenciamás prolongados que los tumores MSS/MSI-L (p = 0,027). No observamos diferencias en la respuestaa quimioterapia con 5-fluorouracilo y leucovorín entre los grupos MSS/MSI-L y MSI-H (p =0,38).CONCLUSIONES: El alto grado de inestabilidad de microsatélites se asocia con determinadas característicaspatológicas, así como con períodos de supervivencia más prolongados para los tumoresde estadios II

BACKGROUND AND OBJECTIVE: Currently, colon cancer is a leading cause of cancer death worldwide.It progresses according to three molecular pathways, named suppressor, mutador andmethylator. Microsatellite instability is a hallmark of the lack of reparation, of DNA mismatchesand it characterizes a subset of colon tumors (unstable tumors, MSI). MSI-H patients (high degreeof microsatellite instability) seem to share clinico-pathological differences with MSS (microsatellitestable) and MSI-L (low degree of microsatellite instability) patients. In this study,associations between high degree of microsatellite instability and pathological (location, mucinouscontent, differentiation grade, stages T3N0, stages II and III) and clinical features (responseto chemotherapy, disease-free survival and overall survival) were evaluated.PATIENTS AND METHOD: 117 patients with sporadic colon cancer were classified into two populations(MSS/MSI-L and MSI-H) by using PCR and electrophoresis of seven microsatellites, accordingto the National Cancer Institute recommendations.RESULTS: MSI-H tumors tended to be located in the right colon (p = 0.022) and were of mucinoushistologic type (p = 0.04). No differences in disease-free survival and overall survival betweengroup of stage II and III patients with MSS/ MSI-L and corresponding ones with MSI-Hcolon cancer were found (p = 0.54, p = 0.37, respectively). Conversely, MSI-H patients withstage II colon cancer had a favourable prognosis (p = 0.027). Nevertheless, response to 5-fluorouracil(5-FU) and leucovorin was similar in MSS/ MSI-L and MSI-H groups (p = 0.38).CONCLUSIONS: MSI-H patients are characterized by certain pathological features; those MSI-Hpatients with a stage II seem to have a better prognosis than MSS/ MSI-L patients

PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors.

Medulloblastoma, which accounts for 20-25% of all childhood brain tumors, is defined as a primitive neuroectodermal tumor (PNET) located in the cerebellum. Supratentorial PNET are less frequent than medulloblastoma. But their clinical outcome is worse than in medulloblastomas. Chromosome 10q contains at least 2 tumor suppressor genes that might play a role in brain tumor development: PTEN and DMBT1. The aim of this study was to compare the status of homozygous deletion and expression of PTEN and DMBT1 genes in PNET primary tumor samples and cell lines. Homozygous deletions of PTEN and DMBT1 were studied in 32 paraffin-embedded PNET samples (23 medulloblastomas and 9 supratentorial PNET) and in 7 PNET cell lines, by differential PCR and by FISH. PTEN homozygous losses were demonstrated in 7 medulloblastomas (32%) and in no supratentorial PNET, while homozygous deletions of DMBT1 appeared in 1 supratentorial PNET (20%) and in 7 medulloblastomas (33%). No homozygous deletion of PTEN or DMBT1 was detected in any of the PNET cell lines either by differential PCR or by FISH. Expression study of the 2 genes was performed in the 7 PNET cell lines by RT-PCR. One PNET cell line lacked PTEN and DMBT1 expression, while 2 medulloblastoma cell lines did not express DMBT1. Our results add some positive data to the hypothesis that supratentorial PNETs and medulloblastomas might be genetically different.