Javier de la Torre

MicroRNAs as prognostic markers in ovarian cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy among women. Over 70% of women with OC are diagnosed in advanced stages and most of these cases are incurable. Although most patients respond well to primary chemotherapy, tumors become resistant to treatment. Mechanisms of chemoresistance in cancer cells may be associated with mutational events and/or alterations of gene expression through epigenetic events. Although focusing on known genes has already yielded new information, previously unknown non-coding RNAs, such as microRNAs (miRNAs), also lead insight into the biology of chemoresistance. In this review we summarize the current evidence examining the role of miRNAs as biomarkers of response and survival to therapy in OC. Beside their clinical implications, we also discuss important differences between studies that may have limited their use as clinical biomarkers and suggest new approaches.

Expression of DNA damage checkpoint protein Hus1 in epithelial ovarian tumors correlates with prognostic markers.

Summary Hus1 and Rad9 are proteins involved in DNA damage checkpoint regulation, which is required for the maintenance of genomic stability. In addition to checkpoint activation, mammalian cells also use apoptosis to eliminate cells with severe DNA damage. Interestingly, Rad9 was shown to be directly involved in apoptosis as well. Despite the knowledge of molecular mechanisms on how Hus1 and Rad9 act in response to DNA damage, little is known about the role of these 2 proteins in cancer progression. In this study, we analyzed the expression of Rad9 and Hus1 in epithelial ovarian tumors and correlated them to clinopathological parameters and apoptotic biomarkers (p53, Bcl-2, and Bax). Histological sections from 114 primary ovarian epithelial tumors were stained with antibodies using the streptavidin-biotin method. In addition, mitotic and apoptotic indices (both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling assay) were also measured. We found that Rad9 expression correlated closely to significance only with the apoptotic and mitotic indices (P = 0.056 and 0.059, respectively). Hus1 levels correlated significantly with the clinicopathologic factors of bad prognosis, including FIGO (International Federation of Gynecology and Obstetrics) stage (P < 0.002) and with the p53 expression (P < 0.001), Bax expression (P < 0.008), mitotic index (P < 0.001), and apoptotic index (P < 0.003).

Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome

OBJECTIVE Clinico-pathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 2003 TNM criteria (T1mic</=1mm) are scarce. Nowadays, we do not know the percentages of Ductal Carcinoma in situ (DCIS) that will progress to invasion and predictive markers are not available. Cyclo-oxygenase type-2 (COX-2) is overexpressed in many human malignant tumours and has been linked to the processes of carcinogenesis, cell survival, invasion and metastasis. Despite the data on elevated COX-2 expression in breast neoplasia, the mechanism of upregulation remains unclear. This study aims to evaluate COX-2 expression in DCIS in comparison to MICB in order to establish the importance of this marker as a predictor of microinvasion and the correlation with Van Nuys classification. STUDY DESIGN A retrospective study was performed on archival paraffin-embedded formalin-fixed tissue samples of DCIS and MICB from women who had undergone surgery. The COX-2 expression was assayed by immunohistochemistry using a specific polyclonal anti-human COX-2 antibody. Expression was scored in a scale 0 (absent) to 4 (strong) based on the extent and intensity of tumour cell staining. RESULTS Fifty-two cases of DCIS and 40 of MICB were studied. In all cases, COX-2 was detected in the cytoplasm of tumour cells, and elevated COX-2 expression was observed in Van Nuys high-grade CDIS cases compared with low and intermediate grades (p<0.05). In addition, enhanced COX-2 expression was significantly higher in DCIS component from MICB patients (82% cases) than in DCIS pure patients (40.4%) (p<0.05). In a multivariate model which includes age, tumour size, mammography, histological grade and COX-2 expression, we found COX-2 positivity to be an independent factor for microinvasion (OR 3.90; 95% CI 1.88-14.3). CONCLUSIONS COX-2 is associated to higher Van Nuys grades of breast CDIS, and could be a molecular marker to identify the cases of DCIS which could progress to MICB. CONDENSATION COX-2 as a molecular marker in microinvasive carcinoma of the breast.

Malignant struma ovarii mimic clear cell carcinoma

IntroductionStruma ovarii are quite unusual lesions that represent less than 3% of all teratomas and its malignant transformation is very uncommon. The clinical manifestations are characteristic of pelvic tumor and the hormonal metabolism is not usually modified. Radiography, employing ultrasound procedures, is the most commonly used pre-surgical detection method but only histological examination makes the diagnosis. The malignance recognition by pathological study not always is easy; in this sense, it requires an exhaustive sampling of the lesion, being specially carefully in some aspects related with malignant transformation such as extending beyond the capsula and involving peripheral tissues. A thyroidal differentiation must be confirmed by immunohistochemical study and other local processes with similar histology should be ruled out. Given the exceptional character of malignant forms, there does not appear to be unanimous agreement on a standard therapy with a somewhat uncertain prognosis.Case reportWe show a case of a 22-year-old patient with an ovarian tumor that was discovered by ultrasound examination and surgically removed. The histologic study revealed struma ovarii with malignant transformation towards follicular carcinoma and unlike previously published cases, had a prevalence of clear cells. The patient was submitted to a second surgical staging intervention, with conservative surgery and follow-up controls being considered given that was a young woman with a desire to have children. Laparoscopy was employed as the best method capable to facilitate shorter convalescence.OutcomeClinical and analytical controls, measuring thyroglobulin levels, has been satisfactory up to the present.

Steroid cell tumor (NOS) of the ovary associated to high levels of CA-125

Hirsutism can be defined as an excessive male-pattern hair growth, typically caused by a state of hyperandrogenism. It can be associated with the signs of virilization, such as breast atrophy, increased muscle bulk, deepening of voice, clitoromegaly, and increased libido [1]. This report describes the case of a 44-year-old woman with a steroid cell tumor, NOS (not otherwise specified), of the ovary. This is a rare tumor of the ovary which raises differential diagnosis with many disorders causing hyperandrogenism. A very interesting element of this case is a very high level of CA-125, never described as associated to this type of tumor.