Factores relacionados con la supervivencia libre de enfermedad en el cáncer de mama / Disease-free survival related factors in breast cancer

Objetivo: Evaluar la relación entre los parámetros clínicos y anatomopatológicos del tumor primario y la supervivencia libre de enfermedad (SLE) en una serie hospitalaria de casos de cáncer de mama invasivo. Material y método: Estudio de cohortes retrospectivo con 635 pacientes diagnosticadas en el Hospital Universitario San Cecilio de Granada entre 1994 y 2006. La información relativa al tumor primario y a la evolución de la enfermedad se recogió mediante revisión de historias clínicas. La identificación de factores relacionados con el riesgo de recidiva y/o metástasis, y la SLE se realizó, a corto (3 y 5 años) y medio plazo (10 años), mediante análisis de regresión de Cox. Resultados: Tras ajustar por edad, tamaño tumoral, afectación ganglionar, grado histológico y expresión de receptores de estrógenos y de progesterona, se relacionan con mayor riesgo de recaída y menor SLE: el tamaño tumoral (3 años: riesgo relativo ajustado 3,00, intervalo de confianza del 95% 1,79-5,03; 5 años: 2,56, 1,65-3,98; 10 años: 2,16, 1,44-3,24), la infiltración ganglionar (3 años: 4,58, 2,42-8,65; 5 años: 3,84, 2,35-6,30; 10 años: 3,08, 2,05-4,61), la invasión linfovascular (5 años: 1,88, 1,16-3,04; 10 años: 2,19, 1,43-3,35), la multifocalidad/multicentricidad (3 años: 2,69, 1,46-4,96; 5 años: 1,90, 1,08-3,35) y p53 (3 años: 2,03, 1,00-4,09). Se relacionan con mayor SLE, la expresión de receptores de progesterona (3 años: 0,48, 0,26-0,89; 5 años: 0,58, 0,35-0,97; 10 años: 0,59, 0,38-0,90). Conclusiones: Las características biológicas del tumor primario permiten identificar pacientes con diferente pronóstico y SLE, pudiendo contribuir a la planificación de estrategias de seguimiento más personalizadas (AU)

Objective: To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. Material and method: We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Results: Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). Conclusions: The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies (AU)

[Disease-free survival related factors in breast cancer]. / Factores relacionados con la supervivencia libre de enfermedad en el cáncer de mama.

OBJECTIVE: To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. MATERIAL AND METHOD: We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. RESULTS: Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). CONCLUSIONS: The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies.

Morphological and immunohistochemical evaluation of ganglion cysts. Cross-sectional study of 354 cases.

UNLABELLED: The aim of this study was to characterize the morphology and immunophenotype of ganglion cysts (GCs) and explore their histogenetic origin. MATERIAL AND METHODS: A cross-sectional morphological and immunohistochemical study of 354 GCs used the following antibody panel: vimentin, specific actin, ß-actin, smooth-muscle actin, smoothelin, h-caldesmon, ß-catenin, desmin, calponin, podoplanin, keratins 5/6, E-cadherin, cyclooxygenase 2 (COX-2), lysozyme, CD10, CD31, CD33, CD34, CD68, Ki-67, and PCNA. Double-blind semi-quantitative analyses were conducted to evaluate the immunopositivity on a 4-point scale. Samples from 10 synovial membranes and 10 scapholunate ligaments were compared. GCs showed a hyalinized wall with mesenchymal spindle cells and were intensely positive for vimentin, actins, h-caldesmon, calponin in all cases and for podoplanin in 53% of cases, suggesting features of early muscle differentiation, without ruling out a myofibroblastic origin. Focal cavity lining of non-synovial flat or raised cells (CD34/CD31/CD10/E-cadherin-negative and podoplanin-positive in 34% of cases) was detected in 93% of cases, showing differential expression with synovial membrane and scapholunate ligament cells. Nuclear positivity for proliferative markers was observed in GC wall cells (258.1±255; 1019.3±316 positive cells/mm², Ki-67 and PCNA, respectively) but positivity for these markers was significantly lower (p⟨0.001 Mann Whitney U-test) in scapholunate ligament samples. CONCLUSION: In this first immunohistochemical study of GCs, focal cellular lining of the cavity was observed in almost all cases, and the immunophenotype was identical to that of GC wall cells. These cells are immunohistochemically different from synoviocytes and scapholunate ligament cells and show characteristics of myofibroblasts or mesenchymal cells undergoing early muscle differentiation.

Expression of smoothelin and smooth muscle actin in the skin.

INTRODUCTION: Smoothelin is a cytoskeletal protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA). OBJECTIVE: To evaluate the expression of smoothelin and SMA in the skin in order to establish specific localizations of smoothelin in smooth muscle cells with high contractile capacity and in the epithelial component of cutaneous adnexal structures. METHODS: Immunohistochemical analysis (smoothelin and SMA) was performed in 18 patients with normal skin. RESULTS: SMA was expressed by the vascular structures of superficial, deep, intermediate and adventitial plexuses, whereas smoothelin was specifically expressed in the cytoplasm of smooth muscle cells of the deepest vascular plexus and in no other plexus of the dermis. The hair erector muscle showed intense expression of smoothelin and SMA. Cells with nuclear expression of smoothelin and cytoplasmic expression of SMA were observed in the outer root sheath of the inferior portion of the hair follicles and intense cytoplasmic expression in cells of the dermal sheath to SMA. CONCLUSIONS: We report the first study of smoothelin expression in normal skin, which differentiates the superficial vascular plexus from the deep. The deep plexus comprises vessels with high contractile capacity, which is important for understanding dermal hemodynamics in normal skin and pathological processes. We suggest that the function of smoothelin in the outer root sheath may be to enhance the function of SMA, which has been related to mechanical stress. Smoothelin has not been studied in cutaneous pathology; however we believe it may be a marker specific for the diagnosis of leiomyomas and leiomyosarcomas of the skin. Also, smoothelin could differentiate arteriovenous malformations of cavernous hemangioma of the skin.

Multifocal intrafollicular granulosa cell tumor of the ovary associated with an unusual germline p53 mutation.

A 23-year-old woman presented with a 7 cm right multicystic mass in the ovary, which corresponded microscopically to an unusual lesion consisting of a multifocal granulosa cell tumor with intrafollicular ('in situ') growth involving two-thirds of mature follicles. Stromal invasion was found in only one area where neoplastic follicles coalesced. Granulosa cells had atypical, bizarre TP53 positive nuclei with hyperchromatism, abundant mitoses and numerous hyaline globules. The contralateral ovary was normal. From the age of 10 years, the patient had a complex medical history of multiple tumors, including telangiectatic osteosarcoma, typical and malignant phyllodes tumor, reticulohistiocytoma of skin, carcinomas of the breast and lipo- and leiomyosarcoma. The female genital tract also harbored myometrial leiomyomas and an early endometrial carcinoma. Retrospective histologic study of all mesenchymal neoplasms in this patient showed, the conspicuous presence of similar bizarre TP53 positive cells with hyaline globules in all the mesenchymal neoplasms. In the genetic study, a germline p53 gene mutation was detected in exon 10, codon 336, generating a stop codon in the oligomerization domain of the protein (E336X). A further p53 mutation was found in exon 7 in the granulosa cell tumor. Mutation occurred de novo since there was no history of tumors in any family members, all of whom had a wild-type p53. Although this patient shows a typical tumor phenotype of Li Fraumeni syndrome, the germline mutation corresponded to a highly unusual mutated domain, which is similar to the one found in childhood malignant adrenocortical tumor; also a rare neoplasm that originates in adrenocortical cells; which are closely related, both functionally and embryologically, to granulosa cells.