Davor Tomas

Impact of the EpCAM expression on biochemical recurrence-free survival in clinically localized prostate cancer

BACKGROUND The epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. The role of EpCAM is not limited to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. OBJECTIVE Several studies investigated EpCAM expression in prostate carcinoma but none of them confirmed its prognostic role. The aim of our study was to investigate EpCAM expression and its relationship with established prognostic features in prostate carcinoma. MATERIALS AND METHODS The study included a cohort of 102 patients treated with radical prostatectomy for clinically localized prostate carcinoma. Immunohistochemistry was performed to evaluate the EpCAM expression in prostate cancer and non-neoplastic prostate tissue. The percentage of positively stained carcinoma and benign glands was examined in the whole mount of the chosen slide. RESULTS The extent of EpCAM expression was significantly higher in malignant than in benign prostatic tissue (P < 0.001). EpCAM expression in prostate cancer was associated with established features indicative of worse prognosis, such as preoperative (P = 0.009) and postoperative (P = 0.004) Gleason score and follow-up time (P < 0.001). Patients with higher preoperative and postoperative Gleason score and short follow-up time had tumors with a significantly higher expression of EpCAM. Negative correlation of follow-up time and EpCAM expression indicated that tumors in patients with biochemical recurrence (BCR) harbored higher EpCAM expression. Moreover, expression of EpCAM was significantly higher in patients with BCR compared with patients without BCR (P < 0.001). Tumors in T3 stage of the disease showed significantly higher EpCAM expression compared with T2 tumors (P = 0.002). Univariate (P < 0.001) and multivariate (P < 0.001) analyses showed that EpCAM expression was a significant predictor of shorter biochemical recurrence free-survival. CONCLUSION Our results confirmed high level of EpCAM expression in prostate cancer and support its potential role in prostatic cancer progression. In addition, EpCAM could serve as an additional prognostic marker for the recognition of patients with an increased risk of disease recurrence that need introduction of secondary therapy.

Primary ovarian leiomyoma associated with endometriotic cyst presenting with symptoms of acute appendicitis: a case report

BackgroundOvarian leiomyoma is a rare benign tumor that accounts for 0.5 to 1% of all benign ovarian tumors. It probably arises from smooth muscle cells in the ovarian hilar blood vessels but there are other possible origins including cells in the ovarian ligament, smooth muscle cells or multipotential cells in the ovarian stroma, undifferentiated germ cells, or cortical smooth muscle metaplasia. Additionally, smooth muscle metaplasia of endometriotic stroma, smooth muscle present in mature cystic teratomas, and smooth muscle in the walls of mucinous cystic tumor may explain their occurrence in the ovary in some cases.Case presentationA 31-year-old woman was admitted to our surgical emergency service with a one-day history of appendicitis-like symptoms. Upon laparotomy, there was a solid, oval left-sided ovarian tumor located behind the uterus. The tumor was sent to the pathology department. A diagnosis of primary ovarian leiomyoma associated with an endometriotic cyst was established.ConclusionThe origin of ovarian leiomyoma is still unresolved. In our case, the tumor probably arose from smooth muscle cells derived from myofibroblasts that originate from metaplastic ovarian stromal cells present in the rim of the endometriotic cyst. Despite its rarity, ovarian leiomyoma should be considered in the differential diagnosis of ovarian spindle cell tumors. Appropriate diagnosis may require additional immunohistochemical analysis in some cases.

Expression and prognostic role of syndecan-2 in prostate cancer

Syndecans are a four-member family of transmembrane heparan sulphate proteoglycans that have different functions in cell signalling, adhesion, cytoskeleton organization, migration, proliferation, and angiogenesis. Several studies investigated the role of syndecan-2 (SDC2) in different carcinomas; however, only one being focused on SDC2 in prostate cancer. SDC2 expression and relationship with established prognostic features were assessed in a cohort of 86 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. SDC2 expression was present in the majority of prostate cancers and absent in only 11.6% of cases. SDC2 expression was also recorded in cells of prostatic intraepithelial neoplasia, whereas normal prostatic epithelial tissue and stroma did not express SDC2. SDC2 overexpression in prostate cancer was significantly associated with established features indicative of worse prognosis such as higher preoperative PSA (P=0.011), higher Gleason score (P<0.001), positive surgical margins (P<0.003), and extraprostatic extension of disease (P<0.003). Moreover, expression of SDC2 was also associated with biochemical disease progression on univariate analysis (P<0.001). Study results supported the potential role of SDC2 in prostatic carcinogenesis and cancer progression. Moreover, SDC2 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression in patients with prostate cancer.

Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma

The aim of this study was to analyse relationship between changes of the stroma and expression of tenascin-C (TN-C) and laminin in prostate carcinoma. Tenascin-C immunostaining was increased, and laminin decreased in carcinomas compared with peritumoural tissue and benign prostate hyperplasia (P<0.05). Statistical analysis confirmed connection between stromal changes and TN-C expression in prostate carcinoma (P<0.05). Gleason pattern 3 carcinomas showed more pronounced stromal reaction and TN-C expression compared with Gleason pattern 4 carcinomas (P<0.05). The main cells in prostate cancer stroma are myofibroblasts that are also responsible for tenascin production. Degradation of laminin was not connected with myofibroblastic stromal changes.

Prognostic value of galectin-3 in primary cutaneous melanoma

Background  Galectin‐3, one of the β‐galactoside‐binding lectins, has been suggested as a marker of disease progression in melanoma patients because of its overexpression observed in recent studies. However, prognostic value of galectin‐3 in primary cutaneous melanoma (PCM) has not been clearly defined.

Periacinar retraction clefting in the prostatic needle core biopsies: an important diagnostic criterion or a simple artifact?

The diagnosis of prostatic adenocarcinoma in needle core biopsy is based on major and supportive criteria. One of the supportive criteria is the presence of retraction clefting around neoplastic glands. We analyzed a series of 137 prostatic cancer cases diagnosed by needle core biopsy to determine the frequency, extent and criteria for periacinar retraction clefting. Clefting was analyzed on ten neoplastic and ten normal glands in three different high power fields. One-third or more glands with clefts affecting more than 50% of circumference were significantly more common in tumors (51.8%) than in benign glands (8%) (P<0.0001). A stricter criterion that designated as positive the cases with at least 50% of neoplastic glands (15 of 30) with clefts that affected more than 50% of circumference revealed clefts in only 15.3% of the malignant cases but none in benign cases (0%) (P<0.0001). Regardless of their extension, 15 or more glands with clefts were also more prominent in malignant cases (86.9%) than in benign cases (20.4%) (P<0.0001). We conclude that periacinar retraction clefting represents a reliable criterion for diagnosis of the prostatic adenocarcinoma, especially in cases with clefts affecting more than 50% of circumference in at least 50% of suspicious glands.

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p = 0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors

In the present study changes of components of Wnt signaling pathway—axin (AXIN1) and beta-catenin (CTNNB1) in a sample of 72 neuroepithelial brain tumors were investigated. AXIN-1 gene was tested by PCR/loss of heterozygosity (LOH). Immunostaining and image analysis revealed the quantity and localization of relevant proteins. Polymorphic marker for AXIN-1, showed LOH in 11.1% of tumors. LOH was distributed to 6.3% of glioblastomas, one was found in neuroepithelial dysembrioplastic tumor and one in medulloblastoma. Down regulation of axin expression and up regulation of beta-catenin were detected in the analyzed tumors. Axin was observed in the cytoplasm in 68.8% of samples, in 28.1% in both the cytoplasm and nucleus and 3.1% had no expression. Beta-catenin was observed mainly in the nucleus and cytoplasm (59.4%). Expression in 34.4% of samples was in the cytoplasm and 6.3% showed no expression. Comparison of mean values of relative increase of axin and beta-catenin showed that they are significantly reversely proportional (P = 0.014). Relative quantity of beta-catenin in patients with gross deletion of AXIN1 was significantly higher in comparison to patients without LOH (P = 0.040). Our results demonstrate that changes of key components of the Wnt signaling play a role in neuroepithelial brain tumors.

Prognostic value of connexin43 expression in patients with clinically localized prostate cancer.

Connexins (Cxs) are a family of transmembrane proteins that build cell-to-cell channels in gap junctions. Gap junctions composed of Cxs have an essential role in intercellular communication, adhesion and cell differentiation. Several studies investigated the role of connexin43 (Cx43) in different carcinomas; however, none investigated its prognostic role in prostate cancer. Cx43 expression and relationship with established prognostic features were assessed in a cohort of 102 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Cx43 expression in prostate cancer was significantly associated with established features indicative of worse prognosis, such as follow-up time (P<0.001) and preoperative PSA (P<0.007). Patients with lower Cx43 expressions in tumours have shorter follow-up time, which indicated shorter disease-free survival and higher preoperative PSA values. Furthermore, tumours with positive surgical margins (P<0.001) showed significantly lower Cx43 expression compared with tumours without this feature. In univariate (P<0.001) and multivariate (P=0.014) analyses, decreased Cx43 expression was found to be a significant predictor of biochemical recurrence free-survival. Study results show the association of decreased Cx43 expression with prostate cancer progression. Moreover, Cx43 could serve as an additional prognostic marker and used together with traditional prognostic markers might help in further stratifying the risk of disease progression in patients with prostate cancer.

Intensity of stromal changes predicts biochemical recurrence-free survival in prostatic carcinoma

Abstract Objective. The reactive stroma of prostate cancer contains a mixture of myofibroblasts and fibroblasts, while fully differentiated smooth-muscle cells are very rare or absent. In experimental prostate cancer models, prostatic stromal cells promote angiogenesis and stimulate prostate tumorigenesis. The aim of this study is to analyse whether the intensity of stromal changes can predict survival in patients with prostatic carcinoma. Material and methods. Stromal reaction was quantified histochemically and imunohistochemically in 50 patients treated with radical prostatectomy for clinically localized prostate carcinoma and its relationship with established prognostic factors was assessed. Results. Kaplan–Meier analysis showed a significant association between the pattern of vimentin and desmin expression and the length of disease-free period; patients with a higher vimentin or lower desmin expression had a shorter disease-free period. On multivariate analysis only vimentin expression (odds ratio 4.06, 95% confidence interval 1.01–16.26, p = 0.049) was a significant predictor of biochemical recurrence. In patients with identical Gleason pattern and Gleason score the level of vimentin expression could identify patients with a higher risk of disease recurrence. Conclusions. Intensity of stromal changes could serve as an independent prognostic factor in the assessment of biochemical recurrence-free survival. Among prostate cancer patients with an identical Gleason score, it could identify patients with a higher risk of biochemical recurrence. Thus, stromal changes and their intensity could serve as a novel marker for the recognition of patients with an increased risk of disease recurrence.