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The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas.

This study was aimed to evaluate the utility of a panel of antibodies, consisting of thyroid transcription factor-1 (TTF-1), p63, and cytokeratins (CK) 5/6 for distinguishing between small cell lung carcinoma (SCLC) and nonsmall cell lung carcinoma, as well as for identifying glandular or squamous differentiation in small tissues obtained by bronchoscopy. Bronchoscopic biopsies of 77 lung carcinoma cases with easily recognizable morphologic features were included in this study. All the cases were immunohistochemically stained for p63, CK5/6 [indicators of squamous cell carcinoma (SCC)] and TTF-1 [indicator of SCLC and adenocarcinoma (AC)]. Although, 28 SCLC displayed TTF-1 positive, p63 negative immunoprofile, most of the SCC (32/39) had the opposite immunoprofile. All of the 10 ACs were negative for p63 and most of them (8/10) were negative for CK5/6. p63 and CK 5/6 seem to be useful for differentiating AC and SCLC from SCC with 100% specificity and 82% sensitivity, 89% specificity and 79% sensitivity, respectively. It seems that to achieve histologic typing of lung cancer as accurate as possible, TTF-1 in combination with p63 and CK 5/6 might be useful components of immunohistochemical analysis of poorly differentiated lung carcinomas in biopsy tissues.

Immunohistochemical detection of pS2 protein and heat shock protein-70 in pancreatic adenocarcinomas. Relationship with disease extent and patient survival.

We investigated pS2 and HSP-70 protein expression in 36 pancreatic adenocarcinomas for their effect on disease extent and patient outcome. The cases were reviewed, histologically diagnosed, typed, graded, and staged. Lymphatic vessel, blood vessel and perineural invasion as well as lymph node, resection margin and adjacent organ involvements were re-evaluated. The standard streptavidin biotin immunperoxidase method was used for immunostaining with pS2 and HSP-70 antibodies. Cytoplasmic staining with both antibodies was scored semiquantitatively. The scores were compared with histopathological prognostic parameters using statistical methods. Standard prognostic parameters and staining scores were tested by survival analysis in terms of their effect on survival. All the tumors showed a positive cytoplasmic reaction with HSP-70 antibody. Seventy-seven percent of the tumors showed positive cytoplasmic staining with pS2 antibody (22.2% +, 13.9% ++ and 41.7% +++). There was a statistically significant difference between HSP-70 staining scores with N status and final stages of the tumors (Chi-square, p = 0.03 and p = 0.026, respectively), while neither direct nor inverse correlation was detected for both parameters. PS2 staining scores showed no statistically significant relationship with tumor grade T, M status, perineural invasion, lymph and blood vessel invasion. In tumors with extensive staining with pS2, tumor stage tended to be low (Chi square, p = 0.024, Kendall Tau-b, r: -0.336, p = 0.036). There was a statistically significant difference and inverse correlation between tumors with extensive pS2 staining and tumors with less intense staining in terms of lymph node metastasis (Chi-square, p = 0.041, Kendall Tau: p = 0.024, r = -0,373). In the R0 resection group, in univariate analysis, we found that with higher scores of HSP-70 staining, the prognosis of the patient tended to improve. (Cox regression, p = 0.013). In multivariate analysis, HSP-70 expression was found to be an independent prognostic factor. We found no relationship between pS2 staining and patient survival.

Prognostic significance of angiogenesis and immunoreactivity of cathepsin d and type IV collagen in high-grade stage T1 primary bladder cancer

OBJECTIVES To assess the prognostic significance of biologic parameters such as angiogenesis, expression of cathepsin D (a lysosomal protease), and degradation of type IV collagen (a basement membrane protein), we studied 20 patients with primary grade III Stage T1 transitional cell carcinoma of the bladder. METHODS Endothelial cells were labeled immunohistochemically using factor VIII-related antigen. The vascular surface density (VSD) and the microvessel number (NVES) were assessed by means of stereology. The tumor tissues were also analyzed by immunohistochemical methods for the expression of cathepsin D and the staining pattern of type IV collagen. RESULTS Eight patients (40%) having either recurrence or progressive disease showed greater NVES and VSD values (P = 0.002 and P = 0.01, respectively) than patients without. The significance of vascular parameters was found to be statistically independent from coexisting carcinoma in situ, bacille Calmette-Guerin (BCG) treatment, tumor size, and number. Additionally, these parameters did not show statistical significance between progressive and recurrent tumors. However, tumors with solid morphologic features had higher VSD values and a significantly greater rate of recurrence or progression (P = 0.01 and P = 0.07, respectively). Tissue from 17 (85%) of 20 tumors showed absent or patchy basement membrane staining for type IV collagen, and 12 (60%) showed strong immunoreactivity for cathepsin D antibody. There were no differences for either molecule with either BCG treatment or other parameters related to prognosis. CONCLUSIONS Angiogenesis may have an independent role in predicting prognosis in grade III Stage T1 bladder carcinoma. Grade III Stage pT1 tumors with solid morphologic features have higher angiogenetic activity and a worse prognosis. Cathepsin D and type IV collagen do not seem to play a role in predicting biologic behavior.

Significance of P-glycoprotein, p53, and survivin expression in renal cell carcinoma.

OBJECTIVES This study addresses the relationship between cell cycle control protein p53, apoptosis inhibitor gene survivin, and chemotherapy resistance protein P-glycoprotein (P-gp) expression, and their prognostic impact in renal cell carcinoma (RCC). METHODS A group consisting of 104 patients with RCC was included from a predefined period of time. The median follow-up was 46 months. Tumor stage was defined according to the 2002 Tumor-Node-Metastasis staging system, and Fuhrman nuclear grading was used. Expression of p53, survivin, and P-gp was assessed on immunohistochemically stained slides of the representative blocks of the tumors. RESULTS A significant relationship was found between survival and histologic subtype (P = 0.001), tumor stage (P = 0.011), and tumor grade (P < 0.001). Although there was inverse correlation between p53 expression and stage (P = 0.014) and grade (P = 0.04), no correlation was observed with the histopathologic type or survival. There was no correlation between survivin expression and histologic subtype, stage, or survival, but there was a significant inverse correlation between survivin expression and tumor grade (P = 0.018). No significant correlation was found between any parameters tested, and P-gp expression. CONCLUSIONS Survivin, P-gp, and p53 expression do not play a role in prognosis of RCC. Our results suggest that survivin expression may be positively regulated by mutant p53 in RCC, and this expression may have an impact on resistance to chemotherapy in RCC.

Expression of p53 and mdm2 and Their Significance in Recurrence of Superficial Bladder Cancer

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Role of Intraoperative US in the Decision for Radical or Partial Nephrectomy

PURPOSE To investigate the effect of intraoperative ultrasonographic (US) findings on the decision for the type of nephrectomy to be performed in patients who had renal tumors that were preoperatively evaluated by using magnetic resonance (MR) imaging, with pathologic results as the reference standard. MATERIALS AND METHODS The institutional review board approved the study protocol, and informed consent was obtained. Between June 2008 and September 2009, 44 patients (25 men, 19 women; mean age, 56.6 years; range, 28-76 years) with 46 renal tumors were prospectively assessed by using intraoperative US examinations to demonstrate tumor relationship with the nontumoral intact parenchyma. Findings at preoperative MR examinations were retrospectively evaluated by two radiologists to determine the type of surgery that would be recommended. The reference standard was results of pathologists review of gross specimens and postoperative reports. The observers assigned their decisions as follows: score group 1, radical nephrectomy should be (should have been) performed; score group 2, partial nephrectomy can be (could have been) attempted; and score group 3, partial nephrectomy should be (should have been) performed. RESULTS Radical nephrectomy was performed in 36 lesions. In all cases, the intraoperative US observer and the pathologist were concordant in the decision that radical nephrectomy versus partial nephrectomy could or should have been performed. MR observers 1 and 2 overcalled the need for radical nephrectomy in seven and four cases, respectively. Compared with pathologic results, the overall correlation of intraoperative US was 0.991, and the correlation for MR observer 1 was 0.786 and that for MR observer 2 was 0.731. CONCLUSION Intraoperative US can be suggested as a valuable examination method in patients with tumors at a central location with suspicious renal sinus extension demonstrated by using MR imaging. The close cooperation of urologist and radiologist in renal tumor work-up could reduce performance of unnecessary radical nephrectomy.

Sonographic Features of Spermatic Cord Leiomyosarcoma

Leiomyosarcoma of the spermatic cord is a rare tumor, with 55 reported cases to date. 1 There are limited reports on the imaging findings, particularly the sonographic appearance of this rare tumor. We report the sonographic and histopathologic features of a case of spermatic cord leiomyosarcoma and discuss the role of sonography in demonstration and diagnosis of the mass.

Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility

The clinical management of tumor patients is often strongly infuenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures in locally corticosteroid-induced Achilles tendinosis: An experimental study on rats

BACKGROUND To determine the effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures, 72 tendons of 36 Wistar rats were injected with betamethasone sodium phosphate. METHODS By the end of fourth week, both tendons were tenotomized and repaired, then the samples were divided into three groups. The first group was left untreated after suturing. Human amniotic fluid was injected to the second and amniotic fluid and membrane were both administered to the third group. Twenty-four tendons were scored at the end of the first week, and 24 at the end of the second week histopathologically, and 24 biomechanically at the end of the third week. RESULTS There was a significant statistical difference only between the histopathological results of Groups 2 and 3 at the first week. CONCLUSIONS Human amniotic membrane and fluid do not add anything to the healing process of Achilles tendon ruptures in the early phase.