Immunostaining Study on the Expression of NF-κB, ER, and PR in Ovarian Serous Carcinoma.

In order to explore whether NF-κB activation correlates to the prognosis, chemoresistance, and sex hormone receptors status in ovarian serous carcinoma, we analyzed the expression of NF-κB, ER, and PR by immunohistochemistry in 72 cases of ovarian serous carcinoma, investigated the association among these markers, and evaluated their relations to clinicopathologic factors and prognosis. The positive rates were 88.9% for NF-κB cytoplasmic expression, 45.8% for NF-κB nuclear expression, 41.7% for ER, and 29.2% for PR. NF-κB nuclear expression was positively correlated with the 4th edition WHO grade (P=0.045) and tumor stage (P=0.001). NF-κB cytoplasmic expression was associated with preoperative serum CA125 level (P=0.015) and ascites (P=0.042). Neither cytoplasmic nor nuclear staining of NF-κB showed any association with survival. PR expression was correlated with tumor stage (P=0.023) and omental metastasis (P=0.022). Omental metastasis occurred more frequently in ER-/PR- tumors (P=0.009). No correlation between NF-κB expression and ER, PR expression was observed. In conclusion, in ovarian serous carcinoma, NF-κB nuclear expression correlated with the 4th edition WHO grade and PR was a favorable prognostic factor for ovarian serous carcinoma.

The prognostic impact of squamous and glandular differentiation for upper tract urothelial carcinoma patients after radical nephroureterectomy.

PURPOSE: To evaluate the association between tumor squamous and/or glandular differentiation and tumor biological characteristics and to validate the impact of these histologic variants on oncologic outcomes of UTUC patients. METHODS: We retrospectively analyzed the data of 687 UTUC patients who underwent radical nephroureterectomy in our institute, from Aug 1, 1999, to Dec 31, 2011. All pathologic sections were reevaluated for histologic differentiation variations (squamous and glandular). The clinicopathological variables of patients were reviewed. RESULTS: Among the 687 UTUC patients in our study, 53 (7.7 %) had squamous differentiation, 20 (2.9 %) had glandular differentiation and 8 (1.2 %) had both histologic variants. Patients with mixed histologic variant tended to have significant larger percentage of sessile tumor architecture (58.0 vs 18.2 %), presence of CIS (7.4 vs 2.3 %), advanced T stage, advanced tumor grade and lymph node metastasis (17.3 vs 6.6 %; all p < 0.05). Patients with squamous and/or glandular differentiation had significant worse cancer-specific survival than pure UTUC patients (p < 0.001), while significant difference of recurrence-free survival between two groups was not observed (p = 0.126). Patients with both squamous and glandular differentiation did not show significantly worse CSS than those with single histologic variant. Univariate analyses revealed that tumor squamous and/or glandular differentiation was a significant factor on survival (p < 0.001). However, the influence did not remain significant after adjusted for other factors in the multivariate analyses (p = 0.076, HR 1.42). CONCLUSIONS: UTUC patients with squamous and/or glandular differentiation are more likely to have aggressive tumor biological features and tend to have worse postoperative outcomes.

Adult renal cell carcinoma with rhabdoid differentiation: incidence and clinicopathologic features in Chinese patients.

Renal cell carcinoma (RCC) with rhabdoid differentiation is a recently described variant of RCC, which has seldom been reported in China. This form of differentiation has been generally associated with a poor prognosis and is often present in tumors with a poorly differentiated morphology. The development of a rhabdoid morphology appears to represent a common dedifferentiation pathway for renal parenchymal malignancies. The aim of this study is to evaluate the incidence and clinicopathologic features of RCC rhabdoid differentiation in Chinese adult patients and to further investigate its origin. We reviewed 723 cases of RCC obtained between January 2012 and March 2014 in Peking University First Hospital. From these cases, 10 (1.4%) were found to have areas of classic rhabdoid morphology. Immunohistochemistry for vimentin, cytokeratin (CK) (pan-cytokeratin (AE1/AE3), CK20, CK5/6, CK7, and CK8/18), RCC, CD10, Pax-2, Pax-8, CD117, desmin, muscle-specific actin, CD68, p53, and Ki-67 was performed in each case using the labeled streptavidin-biotin method. Rhabdoid differentiation was identified in association with clear cell RCC, papillary RCC (II type), and sarcomatoid RCC. We compared the morphologic and immunohistochemical features between rhabdoid and nonrhabdoid components. In our cases, rhabdoid differentiation was characterized by the presence of cohesive large epithelioid cells with abundant pink cytoplasm and central eosinophilic intracytoplasmic inclusions and 1 or more large, oval, eccentric, or irregular nuclei containing prominent nucleoli. Most of the rhabdoid areas showed a solid growth pattern. In our series, RCC with rhabdoid differentiation had an aggressive biological behavior, and rhabdoid components were most likely associated with high-grade tumors of advanced stage. In all cases, the rhabdoid and nonrhabdoid tumoral areas without sarcomatoid differentiation exhibited the very similar immunophenotype as follows: vimentin (+/-), AE1/AE3 (+), CK8/18(+), CK7(+/-), CK5/6 (-), CK20 (-), RCC (focal +), CD10 (focal +), Pax-2 (+), Pax-8 (+), CD117 (+/-), desmin (-), muscle-specific actin (-), and CD68 (-). On p53 and Ki-67 immunohistochemistry, the positive rate of rhabdoid cells for both p53 and Ki-67, similar to sarcomatoid cells, was higher than that of nonrhabdoid tumor cells without sarcomatoid differentiation. Our results indicate that the incidence rate of rhabdoid differentiation in Chinese adult RCC patients is lower than that of foreign reports. We support that the rhabdoid and nonrhabdoid tumor cells originate from the same clone, and the rhabdoid components present high proliferative activity and indicate a poor prognosis.

Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and predicts patient outcomes.

Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.

Defective expression of Protein 4.1N is correlated to tumor progression, aggressive behaviors and chemotherapy resistance in epithelial ovarian cancer.

OBJECTIVE: Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression. METHODS: 4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting. RESULTS: Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p<0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p<0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p=0.004), ascites (p=0.009), omental metastasis (p=0.018), suboptimal debulking (p=0.024), poorly histological differentiation (p=0.009), high-grade serous carcinoma (p=0.001), short progression-free-survival (p=0.018) and poor chemosensitivity to first-line chemotherapy (p=0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines. CONCLUSIONS: 4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.

[Correlation between estrogen receptor status and clinicopathologic parameters in endometrial cancer: a comparative study by immunohistochemistry using different scoring systems].

OBJECTIVE: To compare the efficiency of three different estrogen receptor (ER) immunostaining scoring systems by analyzing the correlation between ER status and clinicopathologic features for prediction of prognosis of patients with endometrial carcinoma (EC). METHODS: ER immunostaining (EnVision method) was performed in 160 type I EC and 39 type II EC paraffin samples and was scored by ASCO/CAP criterion, H-Score and Allred scoring system. Correlation between ER status and clinicopathologic features was statistically analyzed. RESULTS: ASCO/CAP criterion, H-Score and Allred (cutoff point: 4-8) scoring system showed high concordance in the following aspects. In EC patients, ER status was significantly associated with presurgical CA125 levels (P = 0.015, P = 0.007, P = 0.023), histologic grades (all P < 0.01) and PR status (all P < 0.01). In type I EC cohort, ER status was significantly correlated with PR status (P = 0.008, P < 0.01, P < 0.01) and p53 status (P = 0.042, P = 0.001, P < 0.01). As of the predictive value of ER status for type I EC patient age, ASCO/CAP (P = 0.027) and H-Score criteria (P = 0.035) were both superior to Allred score system (P = 0.064). Among well-known predictive clinicopathologic parameters, including FIGO stage, lympho-vascular involvement, lymph node metastasis, depth of myometrial invasion and omental involvement, ASCO/CAP scoring offered a better correlation (P = 0.005, P = 0.002, P = 0.021, P = 0.067, and P = 0.067, respectively) than H-Score (P > 0.05) and Allred scoring system (P > 0.05). CONCLUSIONS: Compared with H-Score and Allred scoring system, ASCO/CAP criterion is more closely correlated with predictive clinicopathologic parameters. Therefore it may be used as a simple, highly efficient prognostic indicator for EC patients in routine practice.

Prevalence and Risk Factors of Prostate Cancer in Chinese Men with PSA 4-10 ng/mL Who Underwent TRUS-Guided Prostate Biopsy: The Utilization of PAMD Score.

PURPOSE: To elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4-10 ng/mL and develop a risk-stratification score model. METHODS: The data of 345 patients who underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volume (PV), magnetic resonance imaging (MRI), and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason Score ≥ 7). RESULTS: The median PSA was 7.15 (IQR 5.91-8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results, and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a "PAMD" score which combined the four factors to categorize patients into three risk groups, and the model performed good predictive sensitivity and specificity. CONCLUSION: The prevalence of prostate cancer in Chinese patients with PSA 4-10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI, and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk-stratification and decision-making.