Molecular Heterogeneity of Endometrioid Ovarian Carcinoma: An Analysis of 166 Cases Using the Endometrial Cancer Subrogate Molecular Classification.

Endometrioid ovarian carcinoma (EOC) has clinical and biological differences compared with other histologic types of ovarian carcinomas, but it shares morphologic and molecular features with endometrioid endometrial carcinoma. To analyze the molecular heterogeneity of EOC according to the new molecular classification of endometrial cancer and to evaluate the prognostic significance of this molecular classification, we have analyzed 166 early-stage EOC by immunohistochemistry for mismatch repair proteins and p53 expression, and by Sanger sequencing for the exonuclease domain of polymerase epsilon (POLE EDM). In addition, we have carried out next-generation sequencing analysis of tumors with POLE EDM mutations to confirm the ultramutated profile. Eight tumors carried POLE EDM mutations and were classified as ultramutated (5%), 29 showed mismatch repair deficiency and were classified as hypermutated (18%), 16 tumors had a mutated pattern of p53 expression and were classified as p53 abnormal (11%), and 114 tumors did not have any of the previous alterations and were classified as no specific type (66%). Five tumors showed >1 classification criteria. The frequencies of ultramutated and hypermutated tumors were lower in EOC compared with the frequency reported in endometrial cancer. Subrogate molecular groups differed in both morphologic features (histologic grade, squamous and morular metaplasia, and necrosis) and immunohistochemical expression of several biomarkers (ARID1A, nuclear ß-catenin, estrogen receptors, Napsin A, and HINF1B). In addition, the number of CD8 tumor-infiltrating lymphocytes was higher in ultramutated and hypermutated tumors. The most commonly mutated genes in the ultramutated group were ARID1A (100%), PIK3R1, PTEN, BCOR, and TP53 (67% each), whereas no mutations were detected in KRAS. Although the prognosis did not differ among subgroups in the multivariate analysis, a trend toward a better prognosis in POLE-mutated and a worse prognosis in p53 abnormal tumors was observed. In addition, this classification could have important therapeutic implications for the use of immunotherapy in tumors classified as ultramutated and hypermutated.

Pharmacogenetic predictors of outcome in patients with stage II and III colon cancer treated with oxaliplatin and fluoropyrimidine-based adjuvant chemotherapy.

Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.

Tumor papilar de la región pineal: a propósito de un caso / Papillary tumor of the pineal region: A case report

Los tumores de la región pineal son raros, y aún menos frecuentes los de morfología papilar. Presentamos un caso de una mujer de 30 años con una tumoración sólido-quística de 2 cm localizada en la región pineal. Histológicamente se trataba de una lesión papilar, citoqueratina positiva. Tras realizar diagnóstico diferencial con otras entidades como el ependimoma papilar, el meningioma papilar, el papiloma/carcinoma de plexos coroideos y el carcinoma papilar metastásico, concluimos que se trataba de un tumor papilar de la región pineal. En la actualidad solo hay 96 casos de esta neoplasia publicados en el mundo; en el presente artículo presentamos un nuevo caso (AU)

Tumours of the pineal region are infrequent but papillary tumours in this location are even rarer. We present a case of a 30 year old woman with a 2 cm solid cystic tumour of the pineal region. Histologically it was a papillary lesion, positive for cytokeratin. Differential diagnoses of papillary ependymoma, papillary meningioma, papilloma/carcinoma of the choroid plexus and metastatic papillary carcinoma were considered, but the results indicated that the final diagnosis was papillary tumour of the pineal region. There are only 96 previous cases of this tumour in the literature to date (AU)

Condrosarcoma de mama: a propósito de un caso / Breast chondrosarcoma: a case report

Los sarcomas primarios de mama constituyen menos del 1% del total de las neoplasias malignas que se diagnostican en la mama. Son lesiones de rápido crecimiento cuyo principal factor de riesgo deriva de la radioterapia previa sobre la zona. Presentamos el caso de una mujer de 55 años, sin antecedentes patológicos previos, con un tumor mamario de 4,5 cm diagnosticado de condrosarcoma de mama tras la exclusión de otras entidades como carcinoma metaplásico, tumor phyllodes maligno, sarcoma del estroma (fusocelular) y osteosarcoma. Se trata de un tumor muy poco frecuente, del que apenas hay casos publicados en la literatura (AU)

Primary breast sarcomas represent less than 1% of all malignant breast neoplasias. The principal risk factor for these fast growing lesions is previous radiotherapy treatment. We present a case of a 55 year-old woman with a 4,5 cm tumour, which was diagnosed as a chondrosarcoma after excluding other possibilities, such as metaplastic carcinoma, malignant phyllodes tumour, stromal sarcoma (spindle cell) and osteosarcoma. Very few cases of this rare tumour have been reported in the literature (AU)

Multiple bone lesions resembling a metastatic origin. An unexpected diagnosis.

Lytic and blastic lesions have been associated to malignant tumours, such as solid cancer (breast cancer, renal cancer, prostate cancer, malignant melanoma or thyroid tumours). Although a mixed pattern with lytic and blastic lesions is due to metastatic tumour, this is not the only possible origin. The following case shows a systematic. This case report shows the number of tests that were made in order to discover the origin of osteolytic and osteoblastic lesions and it is notable that there is not an occult neoplasia on every occasion.