Borislav Spajić

Tumors in kidney Fusion anomalies. Report of five cases and review of the literature

Objective: Fusion anomalies of the kidney are rarely encountered and the association of malignant tumors with such conditions is exceedingly rare. Association of tumors with horseshoe kidney is also uncommon, with fewer than 200 cases having been reported in the literature, and the association of tumors with crossed‐fused ectopia is even rarer, with only four cases having been reported so far. Material and Methods: During the past decade five patients with fusion anomalies have been treated for tumors in our clinic, four of whom had horseshoe kidney and one of whom had crossed‐fused left‐to‐right ectopia. The clinical, diagnostic and operative peculiarities of each case are presented and the recent literature on this topic is reviewed. Results: Two patients were diagnosed with renal cell carcinoma, two had transitional cell carcinoma and one had oncocytoma. Conclusions: The commonest tumor reported in kidney fusion anomalies is renal cell carcinoma, although its reported incidence is no higher than that in the normal population. In the case of transitional cell carcinomas, diagnosis is usually made at an advanced stage. The value of thorough urologic and radiological investigations is stressed. Angiography, whether classical or in combination with multi‐slice CT, is considered essential in order to confirm renal anomalies and the tumor situation and to plan the surgical approach. In our experience, radical nephrectomy with isthmus division via a transperitoneal approach is the treatment of choice.

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.

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.

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.

Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma

The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma

Tomas D, Spajić B, Milošević M, Demirović A, Marušić Z & Krušlin B
(2011) Histopathology58, 447–454
Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma

CD138-positive plasmacytoid urothelial carcinoma of urinary bladder with focal micropapillary features

Both the plasmacytoid and micropapillary types of urothelial carcinoma of the urinary bladder are uncommon, distinct clinical and pathological findings. To date, several reports in the English medical literature have been published on either of these variants. CD138 is commonly used as a marker for tumors of plasma cell origin. However, few authors have described positive immunoreactivity of plasmacytoid cells in urothelial carcinoma. Mixed histological differentiation is thought to be a phenotype of locally aggressive and advanced urothelial carcinoma. Therefore, a precise histopathological diagnosis should be made and awareness of all the entities is crucial. We report a case of CD138-positive plasmacytoid urothelial carcinoma of the bladder with focal micropapillary features. To our knowledge this is the first case of these two rare subtypes of urothelial carcinoma combined in a single cystectomy specimen.

Neuroendocrine breast carcinoma metastatic to renal cell carcinoma and ipsilateral adrenal gland.

We report on a 60-year-old woman with neuroendocrine carcinoma of the left breast metastasizing to renal cell carcinoma (RCC) of the left kidney and to adrenal gland. A yellow, well-circumscribed tumor, 11 cm in largest diameter and limited to the kidney, was found. Histopathology revealed RCC with foci of neuroendocrine differentiation. Solid sheets of hyperchromatic epithelioid cells with high mitotic activity were found between typical clear cells of RCC. These cells were CAM5,2 and E-cadherin focally positive, synaptophysin and NSE weakly positive, CK19 moderately positive, and AE1-AE3 and EMA strongly positive. Chromogranin A, CD10, CK 14, CK 20, HER2 (score 1+), vimentin, and HMB45 were negative. The left adrenal gland contained multiple, separate foci of a tumor composed of neuroendocrine components. Because of the biphasic tumor in the kidney, extensive clinical examination and further analyses were recommended. Tumor in the left breast was revealed. Two months later, the patient underwent mastectomy with axillary lymph node dissection. The tumor was histologically and immunohistochemically similar to the neuroendocrine component within RCC. All axillary nodes were positive. To our knowledge, this is the first case of neuroendocrine breast carcinoma with metastasis to renal cell carcinoma and ipsilateral adrenal gland.

Correlation of vascular endothelial growth factor and hypoxia-inducible factor-1α expression with pathological renal artery changes in patients with renal cell carcinoma

Abstract Objective. The aim of this study was to correlate the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) with pathological renal artery changes in patients with renal cell carcinoma (RCC). A further aim was to correlate intratumoral microvessel density (MVD) with VEGF and HIF-1α expression and prognostic factors for RCC, including tumour necrosis. Material and methods. Formalin-fixed and paraffin-embedded tissue blocks from 150 patients with RCC and 50 patients with non-tumorous kidney diseases were analysed. The control group consisted of specimens from both renal arteries obtained from 25 decedents at routine autopsy (50 cases in total). Immunohistochemistry was performed using primary antibodies to VEGF, HIF-1α and CD31. Results.Pathological renal artery changes were more common in patients with RCC and non-tumorous kidney diseases than in the control group. MVD was higher in the RCCs of patients with pathological renal artery changes. Tumours with higher HIF-1α expression had higher MVD; however, VEGF expression was not associated with MVD. A significant association was also found between MVD and the extent of tumour necrosis, in that less necrotic tumours had higher MVD. No association between renal artery changes and VEGF and HIF-1α expression was established. Conclusion. Considering the results of this study, the evaluation of renal artery changes in forthcoming research on RCC would be helpful for several reasons: to estimate their incidence in a larger number of patients, to clarify their connection with RCC and to reveal their relationship with MVD in RCC.