Ki‐67, mini‐chromosome maintenance 2 protein (MCM2) and geminin have no independent prognostic relevance for cancer‐specific survival in surgically treated squamous cell carcinoma of the penis

Abstract

M.M. and M.B. contributed equally to the present manuscriptWhat's known on the subject? and What does the study add?• Only little and partly contradictory data are currently published about the prognostic role of immunohistochemically detectable proliferation-associated biomarkers in surgically treated squamous cell carcinoma of the penis (SCCP), and no data are available at present about their usefulness for refining the delineation between different Broders' grading categories (e.g. still G2 or just G3 SCCP?). Moreover, the accuracy of various conventional histopathological parameters for predicting cancer-specific survival (CSS) in surgically treated SCCP has not been systematically evaluated yet.• Based on the so far largest study cohort encompassing 158 consecutive patients with surgically treated PSCCs characterised by means of a central histopathological review, our data add the following to the currently available literature: (i) Ki-67, mini-chromosome maintenance 2 protein (MCM2), and geminin indicate a more aggressive behaviour in SCPP but do not represent independent prognostic parameters in the multivariable analysis in terms of CSS, (ii) these three biomarkers are not helpful for refining the delineation between different Broders' grading categories at the immunohistochemical level, and (iii) the conventional histopathological parameters staging, grading, nodal involvement, and lymphovascular invasion are independent prognostic parameters that together achieve a predictive accuracy of 82% for CSS. Objective• To assess the role of cell proliferation-associated biomarkers to predict cancer-specific survival (CSS) in patients with surgically treated squamous cell carcinoma of the penis (SCCP). Patients and Methods• A multicentre study enrolling 158 consecutive patients with surgically treated SCCP was performed. lymphovascular invasion (LVI) and nodal status, whereas geminin expression only correlated with tumour grade.• The 5-year CSS for the entire study cohort was 62%.• Univariable analysis showed a significant prognostic impact of Ki-67 (P = 0.026), MCM2 (P = 0.007), and geminin (P = 0.036).• In multivariable analysis, only pT (hazard ratio [HR] 1.67; P = 0.003) and pN stage (HR 2.62; P = 0.015) as well as tumour grade (HR 1.89; P = 0.036) and LVI (HR 2.66; P = 0.028) were identified as independent prognostic parameters for CSS.• The accuracy of the Cox model for CSS prediction was 0.820 (95% confidence interval 0.741-0.898).

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

“…Our data are also in line with studies that showed an association between increased immunohistochemical expression of AURKB and shorter survival in head and neck [31], laryngeal [32], lung [33], hepatocellular [34], biliary tract [35], endometrial [36], and ovarian cancer [37]. Similarly, our results are consistent with association between high GMNN level and shorter survival in breast [38], penile [39], renal cell [40], and other cancers, reviewed by Kapoor [41] and Petropoulou et al [20].…”

C-reactive protein in urologic cancers

“…Increased genetic expression of p53 and Ki-67 has been linked to the presence of lymph nodes at presentation and a poor prognosis. However, there has been very little in the way of common serum biomarkers that can be utilized as prognostic factors in these patients (May et al, 2013).…”

Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies

“…A high Ki‐67 labeling index is associated with more aggressive behavior. However, it reportedly does not have any prognostic value for cancer‐specific survival or overall survival . In a study by Kayes et al, Ki‐67 expression determined by immunohistochemistry had a significant prognostic impact on overall survival in bivariate analysis.…”

“…However, it reportedly does not have any prognostic value for cancer-specific survival or overall survival. 29,30 In a study by Kayes et al, Ki-67 expression determined by immunohistochemistry had a significant prognostic impact on overall survival in bivariate analysis. Higher levels of Ki-67 expression were associated with poorer clinical outcomes.…”

“…A study by May et al demonstrated that MCM2 and Geminin labeling indices were prognostic indicators and predictors of locoregional metastasis. However, they failed to have a significant, independent prognostic impact on cancer‐specific survival . Kayes et al found a significant prognostic impact of MCM2 on overall survival in univariate analysis.…”