The prognostic significance of tumor budding and the expression of focal adhesion kinase and survivin in lung adenocarcinoma.

OBJECTIVES: Adenocarcinoma is the tumor group with the highest incidence among lung cancers with poor prognosis. Tumor budding (TB) is the migration of single tumor cells or small clusters of cells from the neoplastic epithelium to the invasive front of the tumor. Focal adhesion kinase (FAK) and survivin are considered as poor prognostic factors in several tumors. Hence, we investigated TB, FAK, and survivin expression in lung adenocarcinoma. METHODS: The study included 103 cases of lung adenocarcinoma in the resection materials. In tumoral tissues; TB was counted and scored in one high-power field (HPF), as low if <5 in 1 HPF and high if ≥5 in 1 HPF. FAK and survivin were studied immunohistochemically. RESULTS: The mean number of TB in 1 HPF is 3.96 ± 2.8. Low-grade TB was observed in 45 (43.7 %) and high-grade TB was observed in 58 (56.3 %) patients. There was a positive correlation between TB and pT stage (p = 0.017), clinical stage (p = 0.002), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.045). The 4-year survival rate in patients was 90 % in those with low-grade TB and 60 % in those with high-grade TB (p = 0.001). FAK and survivin expressions were significantly increased in tumors with high-grade TB (p < 0.05). CONCLUSION: A significant correlation was found between the grade of TB and pT stage, clinical stage, lymphovascular and perineural invasion in lung adenocarcinoma. TB can be considered as a histological parameter showing poor prognosis. It is thought that high expression of FAK and survivin also affect the prognosis in these patients by increasing TB.

Microsatellite Instability Status and the Expression of p16 and Cyclin D1 Proteins in Uterine Adenosarcoma and Their Clinicopathological Significance.

OBJECTIVE: Uterine adenosarcoma has low malignant potential, except in cases with sarcomatous overgrowth (SOG) and a high-grade morphology. We here point out the prognostic clinicopathological and immunohistochemical features as well as the microsatellite instability (MSI) status of high- and low-grade adenosarcomas. MATERIAL AND METHOD: In this study, DNA mismatch repair proteins, p16, cyclin D1, ER, PR, and CD10 were examined in uterine adenosarcoma cases using immunohistochemistry. The association between these proteins and clinicopathological parameters was also evaluated. RESULTS: ER, PR and CD10 expressions were lower and weaker in high-grade adenosarcomas with SOG compared to low-grade adenosarcomas without SOG (p < 0.05). p16 positivity was more frequent in high-grade adenosarcomas than low-grade adenosarcomas (p < 0.05). There was no statistically significant difference between cyclin D1 positivity, MSI, and other clinicopathological parameters (p ≥ 0.05). Cyclin D1 positivity and loss of CD10 expression were associated with shorter disease-free survival (DFS). Loss of ER and CD10 expression was associated with shorter overall survival (OS) (p < 0.05). MSI was not associated with DFS or OS (p ≥ 0.05). CONCLUSION: These results suggested that p16 positivity, and loss of ER, PR, and CD10 expression were predictors of high-grade morphology. Additionally, the current study showed that cyclin D1-positive tumors had high recurrence rates; however, no significant relationships were found between MSI and DFS or OS in patients with uterine adenosarcoma. Further investigations are required to determine the importance of p16, cyclin D1, and MSI in uterine adenosarcomas.

Histologic Evaluation of the Effect of Mecsina Hemostopper on Bone Regeneration for Critical-Size Defects.

PURPOSE: Acceleration of the bone healing period and/or increasing the quality of newly formed bone still have great importance in the field of oral and maxillofacial surgery. The aim of this study was to evaluate the effect of isolated liquid Mecsina (herbal extract) and its combination with xenogeneic graft material (bovine bone graft) on bone regeneration. MATERIALS AND METHODS: Full-thickness critical-size defects with 10-mm diameter and 2-mm depth were created on the calvarial bone region in 28 Sprague Dawley male rats. Four groups were generated: Mecsina Hemostopper, Mecsina Hemostopper + graft group, only graft group, and empty control group. On the 28th day following surgery, all animals were sacrificed. The calvarial samples were evaluated both histopathologically and histomorphometrically. RESULTS: According to the histopathologic evaluation result, vascular proliferation was significantly higher in the groups in which Mecsina Hemostopper was used as a single material or in combination with graft material (P < .05). Histomorphometric evaluation showed that trabecular and osteoid thickness were significantly higher in all Mecsina application groups (P < .05). CONCLUSION: Mecsina Hemostopper was found to be an effective agent in increasing cell proliferation and providing more qualified bone formation. The combination of Mecsina and xenogeneic bone graft was found to be one of the most effective augmentation options for critical-size defects in rats. Mecsina Hemostopper could be used to get more qualified bone formation clinically, but more clinical research is needed in the future.

The Role of Combined Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced MRI for Differentiating Malignant From Benign Breast Lesions Presenting Washout Curve.

PURPOSE: The aim of this study is to evaluate the diagnostic performance of combined breast magnetic resonance imaging (MRI) protocol including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with enhancing lesions that demonstrated washout curve and to determine whether applying apparent diffusion coefficient (ADC) cutoff value could improve the diagnostic value of breast MRI. METHODS: The retrospective study included 116 patients with 116 suspicious breast lesions, which showed washout curve on DCE-MRI, who underwent subsequent biopsy. Morphologic characteristics on DCE-MRI and ADC values on DWI were evaluated. Apparent diffusion coefficient values and morphologic features of benign and malignant lesions were compared. Diagnostic values of DCE-MRI and combined MRI, including DCE-MRI and DWI (applying an ADC cutoff value) for distinguishing malignancy from benign lesions, were calculated. RESULTS: Of the 116 breast lesions, 79 were malignant and 37 were benign. The ADC value of malignant tumors (median ADC, 0.72 × 10-3 mm2/s) was significantly lower than that of benign lesions (median ADC, 1.03 × 10-3 mm2/s; P < .000). The sensitivity and specificity of an ADC cutoff value of 0.89 × 10-3 mm2/s were 92% and 95%, respectively. Dynamic contrast-enhanced MRI alone presented 100% sensitivity and 59.4% specificity. Adding an ADC cutoff value of 0.89 × 10-3 mm2/s provided 100% sensitivity and 81% specificity, which would have prevented biopsy for 21.6% of benign lesions without missing any malignancies. CONCLUSION: Applying an ADC cutoff value to DCE-MRI provides an improvement in the diagnostic value of breast MRI for differentiating among lesions presenting washout curve.

Thyroid cancer incidence and clinicopathological differences in patients with end-stage renal failure.

AIM: In the present study we aimed to determine the prevalence of thyroid cancer and the clinicopathological properties of papillary thyroid cancer (PTC) in a patient population undergoing dialysis for end-stage renal failure (ESRF). MATERIAL AND METHODS: We retrospectively reviewed all thyroid ultrasonography (USG) examinations performed between January 2007 and December 2015 to determine the incidence of nodular thyroid disease in ESRF and normal patient populations. For both patient groups, differences between patient and tumor characteristics were evaluated in patients diagnosed to have PTC. RESULTS: Among 29.381 patients who underwent thyroid USG examination, 3.491 were included in the ESRF group (Group 1) and 25.890 in the control group (Group 2). Tyroid cancer was detected in 77 (2.2%) of 3.491 patients in Group 1 and 338 (1.3%) of 25.890 patients in Group 2. Thyroid cancer was significantly more prevalent in patients with ESRF (p<0.001). DISCUSSION: When only patients with papillary thyroid cancer were considered, no significant difference existed between the two groups with respect to the prevalence of PTC, although PTC cases in the ESRF group had a significantly higher rate of aggressive characteristics such as capsule invasion, multifocality, and lymph node metastasis. Whereas thyroid cancer is more common in patients with ESRF compared to normal controls, papillary thyroid cancer was not significantly more prevalent in the ESRF group. CONCLUSIONS: PTC in the ESRF group having more aggressive properties than those in the control group suggests that PTC should be diagnosed earlier in their course, treated more aggressively, and followed more closely in ESRF. KEY WORDS: End-Stage Renal Failure, Fine Needle Aspiration Biopsy, Papillary thyroid cancer.

Effect of Induced Membrane on Guided Bone Regeneration in an Experimental Calvarial Model.

OBJECTIVE: The aim of this study was to evaluate the effect of induced membrane on guided bone regeneration and to compare its effect with poly-tetra-flourur-ethylene (PTFE) membrane and collagen membrane. METHODS: Sixteen white Vienna rabbits were used for experiments. Initially 1 defect was created on the parietal bone of all animals and cement was placed inside the defects. After 8 weeks, the bone cements were removed, without damaging the induced membrane formed in the defect cavity. And then 2 more defects were created. All defects were filled with xsenogenic graft materials and were covered with newly formed induced membrane, d-PTFE membrane and collagen membrane. Eight animals were sacrificed at 4th week and other 8 animals were sacrificed at 8th week and all bone specimens were histologically evaluated. RESULTS: New bone formation and bone marrow ratios were significantly higher in induced membrane and d-PTFE membrane group compared to collagen membrane group (P < 0.05) at 4th week. Mature bone ratios were significantly higher in induced membrane and d-PTFE membrane group compared to collagen membrane group (P < 0.05) at 8th week. The best CD31 value was detected with d-PTFE membrane group at 4th week and with induced membrane at 8th week. CONCLUSION: Induced membrane can act as a strong barrier membrane and stimulate bone regeneration. Induced membrane technique can be accepted as a good alternative for the reconstruction of critical size defects in maxillofacial region.

Diffusion-Weighted Imaging of Breast Cancer: Correlation of the Apparent Diffusion Coefficient Value with Pathologic Prognostic Factors.

OBJECTIVE: The aim was to evaluate relationship between apparent diffusion coefficient (ADC) values with pathologic prognostic factors in breast carcinoma (BC). MATERIALS AND METHODS: 83 patients were enrolled in this study. Prognostic factors included age, tumor size, expression of estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), nuclear grade (NG), lymph node involvement and histologic type. The relationship between ADC and prognostic factors was determined using Independent sample t-test, ANOVA, Pearson correlation and relative operating characteristics (ROC) analysis. RESULTS: There was no significant difference between ADC and prognostic factors, including age, tumor size, ER, HER2 and histologic type. The PR-positive tumors (p=0.03) and axillary lymph node involvement (p=0.000) showed a significant association with lower ADC values. The ADC values were significantly lower in high-grade tumors than low-grade tumors (p=0.000). ROC analysis showed an optimal ADC threshold of 0.66 (×10-3 mm2/s) for differentiating low-grade tumors from high-grade tumors (sensitivity, 85.5%; specificity, 81%; area under curve, 0.90). CONCLUSION: The lower ADC values of BC were significantly associated with positive expression of PR, LN positivity and high-grade tumor. Especially, ADC values were valuable in predicting NG subgroups.

Can strain elastography combined with ultrasound breast imaging reporting and data system be a more effective method in the differentiation of benign and malignant breast lesions?

PURPOSE: To investigate whether a novel method that combines breast imaging reporting and data system (BI-RADS) with strain elastography contributes to diagnostic performance in differentiation of malignant and benign breast lesions. METHODS: In 81 patients, 81 breast lesions were prospectively investigated. Breast lesions were separately evaluated with ultrasonography and strain elastography. While evaluations with ultrasonography were based on 2003 BI-RADS-US, strain elastography evaluations were based on a 5-point scale and strain ratio. Diagnostic performances of ultrasonography, strain elastography, and the combined method were compared. RESULTS: Among 81 lesions, 43 (53.1%) were benign and 38 (46.9%) were malignant. When a cutoff point of category 3 was used, sensitivity, specificity, positive and negative predictive values, and accuracy for BI-RADS were 100, 11.6, 50, 100, and 53%, respectively. When BI-RADS and strain ratio were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 89.5, 93, 91.9, 90.9, and 91.3%, respectively. When BI-RADS and elastography scores were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 86.8, 97.7, 97.1, 89.4, and 92.5%, respectively. CONCLUSIONS: The combination of strain elastography and BI-RADS was found to have better diagnostic performances to diagnose breast lesions than BI-RADS alone.

Role of tumor-associated macrophages in the Hexim1 and TGFß/SMAD pathway, and their influence on progression of prostatic adenocarcinoma.

BACKGROUND: Hexamethylene bisacetamide-inducible protein 1 (Hexim1) regulates transforming growth factor-ß (TGFß) activity and turnover of SMAD proteins in a cyclin-dependent kinase 9-dependent way. It does so specifically through inhibiting function of this enzyme and by inhibiting the transcriptional activity of positive transcription elongation factor b (P-TEFb). Tumor-associated macrophages (TAMs) play a role in the progression of prostate adenocarcinomas. We investigated the clinicopathological significance of Hexim1, TGFß, SMAD2, and SMAD7 expression in prostate adenocarcinoma cells, and assessed associations between TAMs density and these proteins. METHODS: The cases of 100 patients diagnosed with prostate acinar adenocarcinoma who had undergone radical prostatectomy were retrospectively examined. Each was reviewed for Gleason score, cancer stage, and specific histopathological features. Original slides were re-examined, and new slides were prepared and immunostained with Hexim1, TGFß, SMAD2, SMAD7 and CD68. RESULTS: Hexim1 expression was positively correlated with Gleason score, cancer stage, lymphovascular invasion, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Gleason score, cancer stage, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Hexim1 expression and TGFß expression. More advanced cancer stage, lymphovascular invasion, perineural invasion, and extracapsular extension were correlated with strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression, respectively. Strong Hexim1 expression, strong TGFß expression, and mild SMAD7 expression were associated with higher Gleason score. Strong Hexim1 expression was correlated with strong TGFß expression and mild SMAD7 expression. Strong Hexim1 expression, strong SMAD2 expression, and mild expression of SMAD7 were associated with disease progression. Strong SMAD2 expression was associated with shorter disease-free survival. CONCLUSION: The results suggest that greater TAMs density, strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression play important roles in the progression of prostate adenocarcinoma. Further investigation of these proteins will help facilitate the definitive prognosis of prostate adenocarcinomas. Ultimately, these proteins may be therapeutic targets for patients with prostate cancer.

Recurrent Pleomorphic Adenoma of the Submandibular Gland.

Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. Most PAs occur in the parotid (80%), followed by the submandibular gland (10%) and minor salivary and sublingual glands (10%). Submandibular gland PAs usually manifest in the submandibular area as a painless hard mass. Although several recurrent parotid gland PA cases have been reported in the literature, recurrent submandibular gland PA is quite rare. Complete surgical removal of tumor of the submandibular gland and keeping the capsule intact are important to prevent recurrence. Here we present a rare case of submandibular gland PA recurrence that occurred 5 years after the first surgery and methods to prevent recurrence.

Synchronous primary carcinoma in 5 different organs of a female genital tract: an unusual case and review of the literature.

The occurrence of double simultaneous primary cancers of the female reproductive tract is a common event. However, the occurrence of synchronous primary quadruple gynecologic malignancies is extremely rare. In this report, the clinical and pathological findings of a 35-year-old female patient with synchronous primary gynecologic cancers regarding papillary serous carcinoma of the left ovary, microinvasive carcinoma in situ of the left and right uterine tubes, endometrial intraepithelial carcinoma of the endometrium, and endocervical carcinoma in situ of the uterine cervix were presented. To our knowledge, the patient presented is the first case in aspect of accompanying ovarian papillary serous carcinoma to bilateral tubal microinvasive carcinoma in situ, endometrial intraepithelial carcinoma, and endocervical carcinoma in situ of the uterine cervix.