TGFß Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression.

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFß1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFß1 leads NDRG1, downstream of GSK3ß, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFß and GSK3ß inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFß to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFß and GSK3ß.

T1 bladder carcinoma with variant histology: pathological features and clinical significance.

The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.

Activating Transcription Factor 4 Modulates TGFß-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling.

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFß1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFß and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFß and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFß was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFß/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer. Clin Cancer Res; 24(22); 5697-709. ©2018 AACR.

T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-IIα, survivin, and E-cadherin.

High-grade papillary urothelial carcinoma with subepithelial connective tissue invasion (T1HG) is an aggressive disease at high risk of progression after transurethral resection/Bacillus Calmette-Guerin standardized therapy. The European Organization for Research and Treatment of Cancer has identified T1HG bladder carcinoma that is single and ≤3 cm in the largest dimension at first diagnosis as a category in which the prognosis cannot be further stratified based on conventional criteria. This category may benefit from biomarker analysis as a valuable tool to determine the patient's outcome. To further the issue of biomarkers in predicting aggressiveness in single T1HG bladder carcinoma ≤3 cm in greatest dimension at first diagnosis, we have conducted a validation study of the biomarker risk score set previously reported by our group. The study set included immunohistochemical detection of galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, survivin, HYAL-1, and topoisomerase-IIα in 92 randomly selected specimens at participating institutions. Topoisomerase-IIα expression was identified as a predictor of disease-free survival. p16, survivin, and E-CAD expression predicted progression-free survival, but p16 and E-CAD also predicted overall survival. The current study validates a panel of immunohistochemical markers with the potential of being implemented in practice and supports the use of biomarkers in predicting aggressiveness in patients with first diagnosis of single T1HG bladder carcinoma ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment.

[Clear cell renal cell carcinoma metastasized by a breast ductal carcinoma]. / Carcinoma renal de células claras metastatizado por carcinoma ductal de mama.

OBJECTIVE: To report a clear cell renal cell carcinoma recipient of a metastasizing ductal carcinoma of the breast: A tumor-to-tumor metastasis. METHODS: A 71 year-old woman with a past history of breast carcinoma, diagnosed 12 years before, underwent a nephrectomy for an incidental kidney mass found in a routine imaging examination. RESULTS: Histological examination revealed foci of ductal carcinoma of the breast in an otherwise typical clear cell renal cell carcinoma of the kidney. Immunohistochemical examination confirmed a metastasis of an infiltrating breast carcinoma to a clear cell renal cell carcinoma (positive to GATA3, hormonal receptors and mamoglobin) in a clear cell renal cell carcinoma (positive to PAX8, CD10 and vimentin). CONCLUSIONS: Awareness of this phenomenon should always be kept in mind by urologist in patients with a known history of a previous malignancy and by pathologists when finding a renal tumor with an unusual or dimorphic morphology. Immunohistochemistry plays an important role to establish the exact diagnosis.

Carcinoma renal de células claras metastatizado por carcinoma ductal de mama / Clear cell renal cell carcinoma metastasized by a breast ductal carcinoma

OBJETIVO: Comunicar un caso de carcinoma renal de células claras receptor de metástasis provenientes de un carcinoma ductal de mama. Metástasis de tumor a tumor. MÉTODOS: Una mujer de 71 años con historia de un carcinoma de mama, diagnosticado y tratado 12 años antes, fue nefrectomizada por el hallazgo de una masa renal en una revisión rutinaria. RESULTADOS: El examen histológico mostró focos de carcinoma ductal de mama en un típico carcinoma de células claras renal. El estudio inmunohistoquímico confirmó la metástasis de un carcinoma mamario (positivo a GATA 3, receptores hormonales y mamaglobina) en un carcinoma renal de células claras (positivo a PAX 8, CD10 y a vimentina). CONCLUSIONES: Los urólogos deben tener presente este fenómeno al encontrar una masa renal en pacientes con historia previa de un proceso maligno. También los patólogos deben estar alerta en estas situaciones, principalmente si encuentran un tumor renal con una morfología dimórfica o rara. La inmunohistoquímica juega un papel fundamental para establecer el diagnóstico exacto

OBJECTIVE: To report a clear cell renal cell carcinoma recipient of a metastasizing ductal carcinoma of the breast: A tumor-to-tumor metastasis. METHODS: A 71 year-old woman with a past history of breast carcinoma, diagnosed 12 years before, underwent a nephrectomy for an incidental kidney mass found in a routine imaging examination. RESULTS: Histological examination revealed foci of ductal carcinoma of the breast in an otherwise typical clear cell renal cell carcinoma of the kidney. Immunohistochemical examination confirmed a metastasis of an infiltrating breast carcinoma to a clear cell renal cell carcinoma (positive to GATA3, hormonal receptors and mamoglobin) in a clear cell renal cell carcinoma (positive to PAX8, CD10 and vimentin). CONCLUSIONS: Awareness of this phenomenon should always be kept in mind by urologist in patients with a known history of a previous malignancy and by pathologists when finding a renal tumor with an unusual or dimorphic morphology. Immunohistochemistry plays an important role to establish the exact diagnosis

Clinicopathological characteristics and outcome of nested carcinoma of the urinary bladder.

We present the clinicopathological features of 56 cases of the nested variant of urothelial bladder carcinoma. This is an uncommon variant of bladder cancer, recognized by the current WHO classification of urologic tumors. The nested component represented 100 % of the tumor in 24 cases. The architectural pattern of the tumor varied from solid expansile to infiltrative nests characterized by deceptively bland histologic features resembling von Brunn nests. Typical features of high-grade conventional urothelial carcinoma were present in 32 cases. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear enlargement, most frequently seen in deep areas of tumor. The nested component expressed cytokeratins 7, 20, CAM5.2, and high molecular weight (34ßE12), p63, Ki67, p53, p27, and GATA3. Tumor extension was T1 (n = 9), minimally T2 (n = 10), T2a (n = 1), T2b (n = 4), T3a (n = 8), T3b (n = 13), and T4a (n = 11). On follow-up, 36 of patients died of or were alive with disease from 2 to 80 months (mean 21 months). Four patients died of other causes. Eleven other patients remained disease free. Univariate survival analysis showed no differences for nested carcinoma compared with conventional urothelial carcinoma. As in conventional urothelial carcinoma, in nested carcinoma of the bladder pT category defined different survival groups. In summary, nested variant of urothelial bladder carcinoma is typically associated with advanced stage. In samples of limited volume, it may be misdiagnosed as proliferation of von Brunn nests or other nested-like bladder lesions, delaying definitive therapy.

[Late thyroid and pancreas metastases from a clear cell renal carcinoma. Report of two cases]. / Metástasis tardias en tiroides y páncreas de carcinoma renal de células claras. Presentación de dos casos.

OBJECTIVE: To report two cases of late metastases of clear cell renal cell carcinoma. METHODS: Two patients, a male and a female with history of nephrectomy 17 and 16 years before for renal cell carcinomas, presented new tumours in the thyroid and pancreas, which were excised. RESULTS: Pathology reported that both lesions were clear cell tumours and immunohistochemically they were consistent with metastases from clear renal cell carcinomas. CONCLUSIONS: 1) Previous history of any type of carcinoma should suggest the possibility of metastases when facing a thyroid or pancreatic nodule. 2) All-life follow-up should be made, nephrectomy (resection) for a renal cell carcinoma. 3) In the presence of a clear cell tumour of the thyroid or pan-creatic glands, the differential diagnosis must always include metastatic renal cell carcinoma. 4) The treatment of choice is surgical resection.

Metástasis tardías en tiroides y páncreas de carcinoma renal de células claras. Presentación de dos casos / Late thyroid and pancreas metastases from a clear cel renal carcinoma. Report of two cases

Objetivo: Comunicar dos casos de metástasis tardías de carcinoma renal de células claras. Métodos: Dos pacientes, hombre y mujer, con historia de nefrectomía previa hacía 17 y 16 años respectivamente, presentaron nuevos tumores en tiroides y páncreas, que se extirparon. Resultados: La histopatología de ambas lesiones correspondió a tumores de células claras y el estudio inmunohistoquímico fue compatible con metástasis de carcinoma renal de células claras. Conclusiones: 1º) Ante nódulos en tiroides o páncreas, en pacientes con historia previa de cualquier tipo de carcinoma, se debe considerar la posibilidad de una metástasis. 2º) Los pacientes con carcinoma renal de células claras y nefrectomía (resección), deben tener un seguimiento de por vida, con una actitud de alerta a la aparición de nódulos en tiroides o en páncreas. 3º) En presencia de un tumor de células claras en tiroides o en páncreas, se debe incluir la posibilidad de un carcinoma renal metastático en el diagnóstico diferencial. 4º) El tratamiento de elección es la resección quirúrgica (AU)

Objective: To report two cases of late metastases of clear cell renal cell carcinoma. Methods: Two patients, a male and a female with history of nephrectomy 17 and 16 years before for renal cell carcinomas, presented new tumours in the thyroid and pancreas, which were excised. Results: Pathology reported that both lesions were clear cell tumours and immunohistochemically they were consistent with metastases from clear renal cell carcinomas. Conclusions: 1º) Previous history of any type of carcinoma should suggest the possibility of metastases when facing a thyroid or pancreatic nodule. 2) All-life follow-up should be made, nephrectomy (resection) for a renal cell carcinoma. 3) In the presence of a clear cell tumour of the thyroid or pancreatic glands, the differential diagnosis must always include metastatic renal cell carcinoma. 4) The treatmet of choice is surgical resection (AU)

Apoptotic and proliferation indexes in primary superficial bladder tumors.

Whether apoptotic index [AI] and/or Ki-67 labeling index [Ki-67LI] add prognostic information in bladder cancer remains unclear. Mean AI and Ki-67 LI increased with grade and stage in 147 superficial bladder tumors. AI (>1.7%) correlated with tumor size, grade and proliferation. Ki-67 LI (>10%) correlated with higher grade and stage. Tumor size and Ki-67 LI were independent predictors of disease-free and progression-free survival, respectively. Tumor size, patient's age and tumor's recurrence predicted overall survival. We conclude that conventional clinical parameters and Ki-67 LI define risk groups of bladder tumors, while AI has limited value.

Current practice of Gleason grading of prostate carcinoma.

The Gleason grading system remains one of the most powerful prognostic factors in prostate cancer and is the dominant method around the world in daily practice. It is based solely on the glandular architecture performed at low magnification. The Gleason grading system should be performed in needle core biopsies and radical prostatectomy specimens where it shows a reasonable degree of correlation between both specimens, and most importantly, it remains vital in the treatment decision-making process. This review summarizes the current status of Gleason grading in prostate cancer, incorporating recent proposals for the best contemporary practice of prostate cancer grading.

Association of human herpesvirus type 6 DNA with human bladder cancer.

We examined the presence of human herpesvirus type 6 (HHV6) DNA in a series of 74 bladder carcinomas from a Mediterranean population to elucidate their possible role as cofactor in the development of bladder cancer with or without associated human papillomavirus (HPV) infection. HHV-6 type B DNA was present in 5 men (6.8%) out of the 74 tumors investigated; two of them had associated HPV-16 DNA in the same specimen. In one case that had associated urothelial carcinoma in situ, both HHV-6B and HPV-16 DNA were present. In conclusion, the low incidence of HHV-6B in bladder cancer and the ubiquitous nature of HHV-6 infection are more consistent with a bystander role rather than cofactor in the oncogenesis of bladder cancer.

Estudio de la expresión de ciclooxigenasa-2 como factor pronóstico en el cáncer colorrectal esporádico / Cyvlooxygenase-2 expression as a prognostic factor in sporadic colorectal cancer

Introducción. Los objetivos de este estudio fueron investigar la expresión de ciclooxigenasa-2 (COX-2) en células tumorales de cáncer colorrectal y estudiar la COX-2 como factor pronóstico de metástasis a distancia y supervivencia. Pacientes y método. Se ha estudiado de forma retrospectiva una serie de 105 pacientes con cáncer colorrectal esporádico intervenidos en el Servicio de Cirugía General del Hospital Universitario Médico-Quirúrgico de Jaén entre los años 1991 y 1997. Se estudiaron las siguientes características: sexo, localización tumoral, estadio TNM, tipo histológico, grado histológico, invasión venosa e invasión linfática. El tiempo medio de seguimiento fue de 54 meses. Inmunohistoquímica: la inmunotinción para COX-2 se realizó por el método avidina-biotina-peroxidasa y se valoraron la intensidad y la extensión de la tinción. Resultados. La expresión de COX-2 en las células tumorales se consideró positiva en 38 casos (36,2%). No hubo una relación estadísticamente significativa entre la expresión de COX-2 y las características clínicas e histopatológicas estudiadas (p > 0,05). En 14 pacientes (13,3%) se diagnosticaron metástasis a distancia. En el análisis multivariable la expresión de COX-2 no se relacionó significativamente con las metástasis a distancia (harzard ratio [HR] = 0,36; intervalo de confianza [IC] del 95%, 0,07-1,69). La supervivencia media fue de 55 meses. En el análisis multivariable, la COX-2 no se comportó como factor independiente de riesgo de muerte (HR = 0,51; IC del 95%, 0,22-1,21). Conclusiones. La COX-2 no se relacionó significativamente con las características clínicas e histopatológicas del tumor. La COX-2 no fue un factor pronóstico independiente de recurrencia tumoral y supervivencia (AU)

Introduction. The aims of the present study were to investigate cyclooxigenase-2 expression in neoplastic cells from colorectal carcinoma and to study the role of cyclooxigenase-2 expression as a prognostic factor related to distant metastases and survival. Patients and method. A retrospective study of 105 patients with sporadic colorectal cancer was performed. The patients underwent surgery at the General Surgery Department of the University Hospital of Jaén between 1991 and 1997. Several clinicopathological features were recorded: gender, tumor location, TNM stage, histological type and grade and the presence of venous or lymphatic invasion. The mean time of follow-up was 54 months. Immunohistochemistry: cyclooxigenase-2 expression was tested using avidin-biotin-peroxidase immunostaining. Both the intensity and extension of the stain were assessed. Results. Cyclooxigenase-2 expression in neoplastic cells was considered to be positive in 38 cases (36.2%). No statistically significant relationship was found between cyclooxigenase-2 expression and the clinicopathological features recorded (P >.05). Tumor recurrence: Distant metastases were diagnosed in 14 patients (13.3%). Cyclooxigenase-2 did not show a significant relationship with metastases in the multivariate analysis (HR: 0.36; 95% confidence interval [CI]: 0.07-1.69). Survival: Mean survival time was 55 months. Multivariate analysis did not show cyclooxigenase-2 as an independent risk factor of death (HR: 0.51; 95% CI: 0.22-1.21). Conclusions. Cyclooxigenase-2 expression was not significantly related to clinical and histopathological features of the tumors nor was it an independent risk factor of tumour recurrence or survival (AU)

Valor pronóstico del patrón de invasión tumoral en el cáncer colorrectal esporádico / Prognostic value of invasive growth pattern in sporadic colorectal cancer

Introducción. Por patrón de invasión tumoral entendemos el tipo de crecimiento, infiltrante o no infiltrante, de los márgenes del tumor. El objetivo de estudio es valorar el patrón de invasión tumoral (infiltrantes/no infiltrantes) en el cáncer colorrectal como factor pronóstico relacionado con la recidiva tumoral y la supervivencia. Pacientes y método. Se ha estudiado a 105 pacientes con cáncer colorrectal en los que se realizó cirugía radical en el Servicio de Cirugía General de Hospital Universitario Médico-Quirúrgico de Jaén entre los años 1991 y 1997. El tiempo medio de seguimiento fue de 54 meses. En cuanto al patrón de invasión del tumor, se han descrito 2 tipos de crecimiento del margen tumoral: infiltrante y no infiltrante o desplazante. Resultados. El frente invasor del tumor presentaba una configuración infiltrante en 65 casos (62%). Respecto a la recidiva tumoral, en 14 pacientes (13,3%) se diagnosticaron metástasis a distancia. En el análisis univariable, la configuración infiltrante se comportó como un factor de riesgo de metástasis a distancia con significación estadística; sin embargo, en el análisis multivariable no mantuvo la significación estadística. En cuanto a la supervivencia, fallecieron 30 pacientes (28,5%) por causas relacionadas directamente con la enfermedad neoplásica. La super- vivencia media fue de 55 meses. El crecimiento infiltrante fue un factor independiente de riesgo de muerte con significación estadística (harzad ratio = 2,50; intervalo de confianza del 95%, 1,05-5,88). Conclusiones. La configuración infiltrante del patrón de invasión del tumor se relacionó significativamente con el intervalo libre de metástasis. El crecimiento infiltrante fue un factor pronóstico independiente de la supervivencia en el cáncer colorrectal (AU)

Introduction. Invasive growth pattern refers to the type of growth of the tumoral margins, whether infiltrating or noninfiltrating. The aim of the present study was to evaluate the invasive growth pattern (infiltrating/noninfiltrating) in colorectal cancer as a prognostic factor related to tumoral recurrence and survival. Patients and method. We studied 105 patients with colorectal cancer who underwent radical surgery in the General Surgery Department of the Hospital Universitario Médico-Quirúrgico of Jaen between 1991 and 1997. The mean length of follow-up was 54 months. Regarding invasive growth pattern, 2 types of growth have been described: infiltrating and noninfiltrating. Results. Tumoral invasion was infiltrating in 65 patients (62%). Tumoral recurrence: in 14 patients (13.3%) distant metastases were diagnosed. In the univariate analysis, infiltrative pattern was a statistically significant risk factor for distant metastases; however, this factor did not retain statistical significance in the multivariate analysis. Survival: 30 patients (28.5%) died from causes directly related to the neoplastic disease. The mean survival was 55 months. Infiltrating growth pattern was a statistically significant independent risk factor for death (HR = 2.50; 95% CI = 1.05-5.88). Conclusions. Infiltrating growth pattern was significantly related with the disease-free interval before metastases. Infiltrating growth was an independent prognostic factor of survival in colorectal cancer (AU)

Atypical adenomatous hyperplasia (adenosis) of the prostate: DNA ploidy analysis and immunophenotype.

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34beta-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feulgen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular hyperplasia and AAH (p<0.001) and carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel density was different between AAH and carcinoma (p=0.001) but not between nodular hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected panel of antibodies did not discriminate among these 3 entities reliably.

[Cyclooxygenase-2 expression as a prognostic factor in sporadic colorectal cancer]. / Estudio de la expresión de ciclooxigenasa-2 como factor pronóstico en el cáncer colorrectal esporádico.

INTRODUCTION: The aims of the present study were to investigate cyclooxygenase-2 expression in neoplastic cells from colorectal carcinoma and to study the role of cyclooxygenase-2 expression as a prognostic factor related to distant metastases and survival. PATIENTS AND METHOD: A retrospective study of 105 patients with sporadic colorectal cancer was performed. The patients underwent surgery at the General Surgery Department of the University Hospital of Jaén between 1991 and 1997. Several clinicopathological features were recorded: gender, tumor location, TNM stage, histological type and grade and the presence of venous or lymphatic invasion. The mean time of follow-up was 54 months. Immunohistochemistry: cyclooxygenase-2 expression was tested using avidin-biotin-peroxidase immunostaining. Both the intensity and extension of the stain were assessed. RESULTS: Cyclooxygenase-2 expression in neoplastic cells was considered to be positive in 38 cases (36.2%). No statistically significant relationship was found between cyclooxygenase-2 expression and the clinicopathological features recorded (P >.05). Tumor recurrence: Distant metastases were diagnosed in 14 patients (13.3%). Cyclooxygenase-2 did not show a significant relationship with metastases in the multivariate analysis (HR: 0.36; 95% confidence interval [CI]: 0.07-1.69). Survival: Mean survival time was 55 months. Multivariate analysis did not show cyclooxygenase-2 as an independent risk factor of death (HR: 0.51; 95% CI: 0.22-1.21). CONCLUSIONS: Cyclooxygenase-2 expression was not significantly related to clinical and histopathological features of the tumors nor was it an independent risk factor of tumour recurrence or survival.

[Prognostic value of invasive growth pattern in sporadic colorectal cancer]. / Valor pronóstico del patrón de invasión tumoral en el cáncer colorrectal esporádico.

INTRODUCTION: Invasive growth pattern refers to the type of growth of the tumoral margins, whether infiltrating or noninfiltrating. The aim of the present study was to evaluate the invasive growth pattern (infiltrating/noninfiltrating) in colorectal cancer as a prognostic factor related to tumoral recurrence and survival. PATIENTS AND METHOD: We studied 105 patients with colorectal cancer who underwent radical surgery in the General Surgery Department of the Hospital Universitario Médico-Quirúrgico of Jaen between 1991 and 1997. The mean length of follow-up was 54 months. Regarding invasive growth pattern, 2 types of growth have been described: infiltrating and noninfiltrating. RESULTS: Tumoral invasion was infiltrating in 65 patients (62%). Tumoral recurrence: in 14 patients (13.3%) distant metastases were diagnosed. In the univariate analysis, infiltrative pattern was a statistically significant risk factor for distant metastases; however, this factor did not retain statistical significance in the multivariate analysis. Survival: 30 patients (28.5%) died from causes directly related to the neoplastic disease. The mean survival was 55 months. Infiltrating growth pattern was a statistically significant independent risk factor for death (HR = 2.50; 95% CI = 1.05-5.88). CONCLUSIONS: Infiltrating growth pattern was significantly related with the disease-free interval before metastases. Infiltrating growth was an independent prognostic factor of survival in colorectal cancer.

Prognostic factors in survival of patients with stage Ta and T1 bladder urothelial tumors: the role of G1-S modulators (p53, p21Waf1, p27Kip1, cyclin D1, and cyclin D3), proliferation index, and clinicopathologic parameters.

We studied 159 cases of superficial (stage Ta or T1) bladder tumors to determine the significance on survival of a subset of regulators of transition from G1 to S phase of the cell cycle (p53, p21Waf1, p27Kip1, cyclin D1, cyclin D3) and tumor proliferation (Ki-67 [MIB-1]). Clinical findings (patient age, sex, tumor size, grade, stage [Ta or T1]) were included in the analysis. Univariate analysis revealed association of tumor size (P = .0353), grade in stage Ta tumors (P = .0074), cyclin D1 expression (P = .0182), and Ki-67 index (P = .0033) with disease-free survival and of tumor size (P = .0005), stage (P = .0494), cyclin D3 expression (P = .0105), and Ki-67 index (P = .0272) with overall survival. Cox multivariate analysis revealed cyclin D1 expression and high proliferation index (disease-free) and tumor size, cyclin D3 expression, and high proliferation index (overall survival) as independent predictors. Results suggest that alterations of the progression from the G1 to S phase of the cell cycle are common in papillary urothelial bladder tumors. High tumor proliferation, expression of cyclins D1 and D3, and tumor size at diagnosis might be relevant predictors of survival in patients with stage Ta and T1 bladder urothelial tumors.

Sclerosing adenosis of the prostate. Histologic features in needle biopsy specimens.

Sclerosing adenosis of the prostate is a pseudoneoplastic lesion that can mimic prostate cancer. Because the lesion is more common in the transition zone, which is only rarely sampled in needle biopsy, it is uncommon to see examples of this lesion in biopsy specimens. Because sampling of the transition zone of the prostate is likely to become more frequent, practicing surgical pathologists must be aware of the morphologic features of sclerosing adenosis of the prostate in needle biopsy specimens, in order to avoid misinterpretation of sclerosing adenosis of the prostate, a benign lesion, as prostate adenocarcinoma. We report the morphologic findings of sclerosing adenosis of the prostate in 3 needle biopsy specimens from 2 patients diagnosed as having sclerosing adenosis. We found a combination of histologic (mainly a cellular myxoid stroma and a double-cell population of acinar cells) and immunohistochemical features demonstrating a continuous basal cell layer with myoepithelial differentiation to be diagnostic.