Comparative analysis of GOLPH3 expression in lymph node-positive prostate cancer: immunohistochemistry staining patterns and clinical significance

IntroductionProstate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression.MethodsThe study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed.ResultsA positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP – the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05).ConclusionGOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes

Diminishing the Gender-Related Disparity in Survival among Chemotherapy Pre-Treated Patients after Radical Cystectomy—A Multicenter Observational Study

There is a well-documented problem of inferior outcome of muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) in women. However, previous studies were conducted before neoadjuvant chemotherapy (NAC) was widely adopted to multidisciplinary management of MIBC. In our study, we assessed the gender-related difference in survival between patients who received NAC and those who underwent upfront RC, in two academic centers. This non-randomized, clinical follow-up study enrolled 1238 consecutive patients, out of whom 253 received NAC. We analyzed survival outcome of RC according to gender between NAC and non-NAC subgroups. We found that female gender was associated with inferior overall survival (OS), compared to males (HR, 1.234; 95%CI 1.046–1.447; p = 0.013) in the overall cohort and in non-NAC patients with ≥pT2 disease (HR, 1.220 95%CI 1.009–1.477; p = 0.041). However, no gender-specific difference was observed in patients exposed to NAC. The 5-year OS in NAC-exposed women in ≤pT1 and ≥pT2 disease, was 69.333% 95%CI (46.401–92.265) and 36.535% (13.134–59.936) respectively, compared to men 77.727% 95%CI (65.952–89.502) and 39.122% 95%CI (29.162–49.082), respectively. The receipt of NAC not only provides downstaging and prolongs patients’ survival after radical treatment of MIBC but may also help to diminish the gender specific disparity

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group

Prognostic and Therapeutic Role of CD15 and CD15s in Cancer

CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These cancers include renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma. The biological role of CD15 is interaction with E-, L- and P-selectins (adhesion molecules), allowing for adhesion with endothelial cells. In this way, cancer cells start to interact with the endothelia of blood vessels and consequently move out from the blood flow to the surrounding tissues. Blockage of the antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibody-based therapies. CD15 may serve as a prognostic marker for patients and there are high hopes for its use in the immunotherapeutic treatment of tumours. CD15s is a sialyl derivative of CD15 that possesses its own unique characteristics. Its soluble form may act as a competitive inhibitor of the interaction of cancer cells with epithelial cells and thus disallow migration through the vessels. However, the prognostic relevance of CD15 and CD15s expression is very complex. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews its significance for clinical applications

Diminishing the Gender-Related Disparity in Survival among Chemotherapy Pre-Treated Patients after Radical Cystectomy—A Multicenter Observational Study

There is a well-documented problem of inferior outcome of muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) in women. However, previous studies were conducted before neoadjuvant chemotherapy (NAC) was widely adopted to multidisciplinary management of MIBC. In our study, we assessed the gender-related difference in survival between patients who received NAC and those who underwent upfront RC, in two academic centers. This non-randomized, clinical follow-up study enrolled 1238 consecutive patients, out of whom 253 received NAC. We analyzed survival outcome of RC according to gender between NAC and non-NAC subgroups. We found that female gender was associated with inferior overall survival (OS), compared to males (HR, 1.234; 95%CI 1.046–1.447; p = 0.013) in the overall cohort and in non-NAC patients with ≥pT2 disease (HR, 1.220 95%CI 1.009–1.477; p = 0.041). However, no gender-specific difference was observed in patients exposed to NAC. The 5-year OS in NAC-exposed women in ≤pT1 and ≥pT2 disease, was 69.333% 95%CI (46.401–92.265) and 36.535% (13.134–59.936) respectively, compared to men 77.727% 95%CI (65.952–89.502) and 39.122% 95%CI (29.162–49.082), respectively. The receipt of NAC not only provides downstaging and prolongs patients’ survival after radical treatment of MIBC but may also help to diminish the gender specific disparity

Diagnostic Value of Radio-Guided Sentinel Node Detection in Patients with Prostate Cancer Undergoing Radical Prostatectomy with Modified-Extended Lymphadenectomy

Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability of the radio-guided SLN detection technique for perioperative localization of LNs metastases as well as to map lymphatic drainage patterns of the prostate. Methods. Forty-three patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging underwent radical prostatectomy with modified-extended pelvic lymph node dissection (mePLND). A day before the planned surgery, a Tc-99m nanocolloid was injected into the prostate under the control of transrectal ultrasonography (TRUS). Preoperative single-photon emission computed tomography (SPECT-CT) imaging and intraoperative gamma-probe were used to identify SLNs. All positive lesions were excised, followed by mePLND. The excised lymph nodes (LNs) were then submitted for histopathological examination, which was used as a reference for the calculation of diagnostic parameters of the SLN technique for SPECT-CT and the intraoperative gamma-probe. Results. In total, 119 SLNs were detected preoperatively (SPECT-CT) and 118 intraoperatively (gamma-probe). The study revealed that both SLN detection techniques showed a sensitivity of 90% and a specificity of 6.06%. The negative predictive value (NPV) was 66.67%. SLN technique would have correctly staged nine of 10 patients, which is the same result as in the case of limited LND. However, it allowed the removal of all metastatic nodes only in four of them. SLND would have comprised 69.7% of preoperatively detected LNs, and removed 13 out of 19 positive LNs (68.42%), respectively. Conclusions. Radio-guided SLND has a low diagnostic rate and is a poor staging tool. ePLND remains the gold standard in nodal metastases assessment in PCa. Our study indicates that lymphatic drainage of the prostate and actual metastasis routes may vary significantly