The Rho family of GTPases are involved in actin cytoskeleton organization and associated with carcinogenesis and progression of human cancers. We investigated the roles of Rho family GTPases, prototypes RhoA, Rac1, and Cdc42, and the major downstream targets of RhoA, ROCK-I, and ROCK-II in testicular cancer. We quantified protein expression in paired tumor and nontumor samples from surgical specimens from 57 consecutive patients with testicular germ cell tumors using Western blotting. Protein expression of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was significantly higher in tumor tissue than in nontumor tissue (P < 0.0001). Expression of protein for RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was greater in tumors of higher stages than lower stages (P < 0.0001, P < 0.001, P < 0.001, P < 0.0001, P < 0.0001, respectively). Within stage II nonseminoma (31 patients), protein levels of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 in the primary tumor were lower in the group of 24 patients with no evidence of disease after therapy compared with 7 patients with disease that was refractory/recurrent (P < 0.05). Rho family GTPases may be involved in the progression of testicular germ cell tumors.

Summary The p27Kip1 (p27) protein is a cyclin-dependent kinase inhibitor of the transition from G1 to S phase. It has been reported that decreased p27 protein level is a negative prognostic indicator in human tumours including bladder cancer. We studied the relationship between protein levels of p27, cyclin E and Ki-67 and clinicopathological features of 145 consecutive Japanese patients with transitional cell carcinoma of the bladder using immunohistochemical staining. Low protein levels of p27 were associated with low staining of cyclin E (P = 0.0302), high Ki-67 index (P = 0.0306), poorly differentiated grade (P = 0.0006), muscle invasion (P = 0.0019) and lymph node metastsis (P = 0.0002). Low staining of cyclin E and high Ki-67 index correlated with poorly differentiated grade, muscle invasion and lymph node metastsis. Cyclin E protein levels was inversely related with Ki-67 index (P = 0.0002). Kaplan-Meier plots of survival rate in patients with low versus high p27 staining showed that low protein levels of p27 were associated with a shortened disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Similarly, low staining of cyclin E and high Ki-67 index correlated with a shortened disease-free and overall survival. On multivariate analysis using Cox proportional hazards model, low protein levels of p27 and high Ki-67 index were independent predictors of shortened disease-free (P < 0.0001, P = 0.0031, respectively), and low protein levels of p27, low staining of cyclin E and high Ki-67 index of overall survival (P = 0.0017, P = 0.0009, P = 0.0003, respectively). In superficial bladder tumours (Ta, T1; 86 patients), significant correlations were observed between low p27 staining and high Ki-67 index and early recurrence (P = 0.0048, P = 0.0178, respectively). Among the recurrenced superficial tumours (35 patients), the tumours which remained at a low stage showed high protein levels of p27 and cyclin E, and the tumours which progressed to invasive disease showed a gradual decrease in p27 and cyclin E protein levels over time. Our findings suggest that decreased protein levels of p27 and cyclin E play a role in the progression of bladder cancer and to evaluate these protein levels may be useful in management of the diseases.

Objective To determine the significance of p27Kip1 (p27) for tumour behaviour and prognosis of patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter. Patients and methods Using immunohistochemical staining, the relationship was evaluated between p27 protein level (low  < 50%, high > 50%) and the Ki‐67 labelling index (low  < 30%, high > 30%) and clinicopathological features of 37 consecutive Japanese patients with TCC of the renal pelvis and ureter. Results Low levels of p27 correlated with higher tumour stage (P < 0.05) and positive lymph node metastases (P < 0.05). There was no significant association between p27 staining and the grade and tumour proliferation as assessed by the Ki‐67 index. A high Ki‐67 index correlated with higher grade and stage (P < 0.05). Kaplan‐Meier plots of survival rate in patients with low or high p27 staining showed that low levels correlated with a shorter disease‐free and overall survival (P < 0.001 and P < 0.01, respectively). Similarly, patients with a high Ki‐67 index had lower disease‐free and overall survival than those with a low Ki‐67 index (P < 0.01 and P < 0.05, respectively). The Cox proportional hazards model showed that a low level of p27 was an independent predictor of a shorter disease‐free (P < 0.01) and overall survival (P < 0.05) on univariate analysis, but not of overall survival on multivariate analysis. A high Ki‐67 index was an independent prognostic marker for shorter disease‐free survival on univariate and multivariate analysis (P < 0.01) and for overall survival on multivariate analysis (P < 0.05). In those with a high Ki‐67 index, increased p27 staining was associated with a better prognosis than decreased staining for disease‐free and overall survival (log‐rank test, P < 0.01 and P < 0.05, respectively). Conclusions The finding that a low level of p27 is associated with tumour invasion and unfavourable prognosis indicates that p27 may be a useful prognostic marker for survival in upper urinary tract cancer.

Background: The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC-positive patients. Patients and Methods: This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC-positive had three or more suspicious LNs on US imaging was examined. Results: The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false-negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNACpositive had three or more metastatic LNs. In the FNAC-positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging. Conclusion: Patients with positive cytology were more likely to have ≥3 positive LNs compared to false-negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.

Introduction The purpose of this study was to clarify the clinicopathological features of patients with false‐negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. Methods Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. Results A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non‐SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. Conclusions The false‐negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false‐negative FNAC results.