Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Breast lesions with myoepithelial phenotype.

Myoepithelial cells (MECs) constitute a continuous layer of cells surrounding the breast glands, localised between the epithelial cells (ECs) and the basal membrane. MECs play important roles in normal mammary gland as they produce basal membrane and stimulate secretion. During neoplastic transformation, MECs act as a barrier preventing stromal invasion. MECs themselves can undergo a great variety of changes, ranging from hyperplastic to metaplastic, to neoplastic, and giving rise to a wide spectrum of morphological pictures sometimes difficult to interpret on routine diagnoses. Several benign and malignant breast tumours can present features of MECs differentiation. As these latter tumours are quite infrequent, the purpose of the present study is to offer a review of the morphological spectrum of MECs lesions, with correlations to prognosis.

The value of MRI contrast enhancement in biopsy decision of suspicious mammographic microcalcifications: a prospective multicenter study.

OBJECTIVES: To investigate the inclusion of breast MRI in radiological assessment of suspicious, isolated microcalcifications detected with mammography. METHODS: In this prospective, multicenter study, cases with isolated microcalcifications in screening mammography were examined with dynamic contrast-enhanced MRI (DCE-MRI) before biopsy, and contrast enhancement of the relevant calcification localization was accepted as a positive finding on MRI. Six experienced breast radiologists evaluated the images and performed the biopsies. Imaging findings and histopathological results were recorded. Sensitivity, specificity, NPV, and PPV of breast MRI were calculated and compared with histopathological findings. RESULTS: Suspicious microcalcifications, which were detected by screening mammograms of 444 women, were evaluated. Of these, 276 (62.2%) were diagnosed as benign and 168 (37.8%) as malignant. Contrast enhancement was present in microcalcification localization in 325 (73.2%) of the cases. DCE-MRI was positive in all 102 invasive carcinomas and in 58 (87.9%) of 66 DCIS cases. MRI resulted in false negatives in eight DCIS cases; one was high grade and the other seven were low-to-medium grade. The false-negative rate of DCE-MRI was 4.76%. The sensitivity, specificity, PPV, and NPV for DCE-MRI for mammography-detected suspicious microcalcifications were 95.2%, 40.2%, 49.2%, and 93.3%, respectively. CONCLUSIONS: In this study, all invasive cancers and all DCIS except eight cases (12.1%) were detected with DCE-MRI. DCE-MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are of low-to-medium grade. KEY POINTS: • All invasive cancer cases and 87.8% of all in situ cancer cases were detected with MRI, showing a low false-negative rate of 4.7%. • Dynamic contrast-enhanced MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are predominantly low-to-medium grade. • If a decision for biopsy were made based on MRI findings in mammography-detected microcalcifications in this study, biopsy would not be performed to 119 cases (26.8%).

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01]. CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

Diagnostic performance of diffusion tensor imaging parameters in breast cancer and correlation with the prognostic factors.

PURPOSE: To evaluate the diagnostic performances of the diffusion tensor imaging (DTI) parameters in the diagnosis of breast cancer and to investigate the variations in DTI parameters according to the breast cancer biomarkers. MATERIALS AND METHODS: At 3.0 Tesla (T), DTI was performed in 85 patients with 92 enhancing breast lesions. λ1 , λ2 , λ3 , mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy (FA), relative anisotropy (RA), and geodesic anisotropy (GA) were studied and compared with diffusion-weighted imaging-derived apparent diffusion coefficient. Lesions were analyzed according to BIRADS lexicon. Logistic regression models were constructed to determine the contribution of DTI to the specificity and the accuracy of DCE-MRI. Breast cancer biomarkers; estrogen receptor (ER), HER-2 status, and Ki-67 were correlated with DTI in malignant cases. RESULTS: Malignant lesions exhibited significantly lower MD, RD, λ1 , λ2 , λ3 and higher FA, RA, GA values (P < 0.001). Logistic regression models showed that MD, RD, λ1 , λ2 , λ3 , FA, and RA increase the specificity of the DCE-MRI (from 83.0% to 89.4-93.6%; P < 0.05). Higher RD, λ2 , λ3 and lower FA, RA, and GA values were observed in ER-negative breast cancer (P < 0.05). Ki-67 showed significant, negative correlation with FA, RA, GA, λ1 -λ3 and λ1 -λ2 (r = -0.336 to -0.435; P < 0.05). CONCLUSION: Besides its ability to differentiate malignant breast lesions, DTI improves the specificity of conventional 3.0T breast MRI and shows correlation with biomarkers ER and Ki-67. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:660-672.

Volume Navigation Technique for Ultrasound-Guided Biopsy of Breast Lesions Detected Only at MRI.

OBJECTIVE: The purpose of this study is to assess the utility of a volume navigation technique (VNT) for ultrasound-guided biopsy of MRI-detected, but sonographically ambiguous or occult, breast lesions. SUBJECTS AND METHODS: Within a recruitment period of 13 months (January 1, 2014, through February 1, 2015), 22 patients with 26 BI-RADS category 4 or 5 lesions that were detected at MRI but missed at second-look ultrasound were reimaged using a rapid sequence and a flexible body coil in a 3-T MRI scanner. Patients were supine, with three skin markers placed on the breasts. MRI volume data were coregistered to real-time ultrasound in a dedicated platform, and MRI-detected lesions (six masses, 11 nonmass enhancements, eight foci, and one architectural distortion) were sought using VNT-guided ultrasound. Five needle biopsy specimens were obtained either from each sonographically detected lesion (n = 11) or from VNT-guided sonographically localized breast volume corresponding to the MRI-detected, but still ultrasound-occult, lesions (n = 15). RESULTS: Histopathologic analysis revealed 18 benign and six malignant lesions. The remaining two lesions, both of which appeared as masses at MRI, were high risk and were upgraded to carcinoma after excisional biopsy. All malignant lesions underwent curative surgery; the final histopathologic diagnoses remained unchanged. Of the six malignant lesions, one was a mass, three were nonmass enhancements, and two were enhancing foci at MRI. Three malignant lesions were occult at ultrasound, and three were discerned as subtle hypoechoic changes. No benign lesion was sonographically visualized as a mass, and none progressed, with 56% disappearing at MRI performed during the follow-up period (mean, 14 months). CONCLUSION: Coregistration of MRI and real-time ultrasound enables sonographic localization of breast lesions detected at MRI only. VNT is a feasible alternative to MRI-guided biopsy of ultrasound-occult breast lesions.

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.

Changes in 18F-FDG-PET/CT tumor metabolism are not consistent with pathologic complete response in hormone-positive breast cancer.

PURPOSE: Current evaluation of response to neoadjuvant chemotherapy (NAC) shows that it could achieve pathological complete response (pCR). The purpose of this study was to assess the consistency of maximum uptake values (SUVmax) changes and pCR in hormone-positive locally advanced breast cancer (LABC). METHODS: Ninety hormone-positive LABC patients treated at Marmara University Medical Oncology Clinic, Istanbul, Turkey, between 2009 and 2015 were retrospectively studied. All eligible patients (n=5) received NAC (4-8 cycles) and were evaluated for pCR. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG- PET/CT) scan was performed before and after the completion of NAC. The relative changes of SUVmax both in the primary tumor and the axilla were assessed for consistency with pCR. RESULTS: The patient median age was 46 years (range 26- 76). The patients 13.7% achieved pCR. Values of >50% (n=40) and <50% (n=11) SUVmax changes were not associated with pCR (15% and 18% respectively) (p=1.00). Patients with >75% SUVmax changes could achieve pCR of 20%. Interestingly, most patients with complete metabolic response did not achieve pCR (81%). The difference of the Ki67 levels before and after NAC, tumor localization, HER- 2 positivity, menopausal status, grade of differentiation, lymphovascular and perineural invasion were not associated with pCR. CONCLUSION: SUVmax changes in later cycles of NAC as commonly practised in oncology clinics were not consistent with pCR (p=1.0). Complete metabolic response may not be associated with pCR in hormone-positive LABC. However, almost 80% of patients had >50% decrease in SUVmax and may still have a chance for conservative surgery and less postoperative morbidity. Therefore, 18F-FDG-PET/CT may still have a role to evaluate the tumor response with a need of larger studies and analysis for cost-effectiveness.

Quantitative differentiation of breast lesions at 3T diffusion-weighted imaging (DWI) using the ratio of distributed diffusion coefficient (DDC).

PURPOSE: To investigate the accuracy of diffusion coefficients and diffusion coefficient ratios of breast lesions and of glandular breast tissue from mono- and stretched-exponential models for quantitative diagnosis in diffusion-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: We analyzed pathologically confirmed 170 lesions (85 benign and 85 malignant) imaged using a 3.0T MR scanner. Small regions of interest (ROIs) focusing on the highest signal intensity for lesions and also for glandular tissue of contralateral breast were obtained. Apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were estimated by performing nonlinear fittings using mono- and stretched-exponential models, respectively. Coefficient ratios were calculated by dividing the lesion coefficient by the glandular tissue coefficient. RESULTS: A stretched exponential model provides significantly better fits then the monoexponential model (P < 0.001): 65% of the better fits for glandular tissue and 71% of the better fits for lesion. High correlation was found in diffusion coefficients (0.99-0.81 and coefficient ratios (0.94) between the models. The highest diagnostic accuracy was found by the DDC ratio (area under the curve [AUC] = 0.93) when compared with lesion DDC, ADC ratio, and lesion ADC (AUC = 0.91, 0.90, 0.90) but with no statistically significant difference (P > 0.05). At optimal thresholds, the DDC ratio achieves 93% sensitivity, 80% specificity, and 87% overall diagnostic accuracy, while ADC ratio leads to 89% sensitivity, 78% specificity, and 83% overall diagnostic accuracy. CONCLUSION: The stretched exponential model fits better with signal intensity measurements from both lesion and glandular tissue ROIs. Although the DDC ratio estimated by using the model shows a higher diagnostic accuracy than the ADC ratio, lesion DDC, and ADC, it is not statistically significant. J. Magn. Reson. Imaging 2016;44:1633-1641.

Use of a Volume Navigation Technique for Combining Real-Time Ultrasound and Contrast-Enhanced MRI: Accuracy and Feasibility of a Novel Technique for Locating Breast Lesions.

OBJECTIVE: The objective of this study was to evaluate the accuracy of the volume navigation technique for combining real-time ultrasound and contrast-enhanced MRI (CE-MRI) of breast lesions. SUBJECTS AND METHODS: Thirty-eight women with single breast lesions underwent 3-T MRI. A 3.5-minute CE-MRI sequence was used, as was a flexible body coil. Patients underwent imaging in the supine position, with three markers placed on their breasts. Real-time sonographic images were coregistered to the preloaded breast CE-MRI volume by coupling skin markers, with the use of an electromagnetic transmitter positioned next to the subjects. The transmitter detected the spatial positions of the two electromagnetic sensors mounted on the transducer bracket. After this fusion process in 3D space was completed, divergences in the location of the center of each lesion on CE-MRI and ultrasound images were analyzed. RESULTS: The mean lesion size was 17.4 mm on ultrasound and 17.9 mm on MRI, whereas the mean (± SD) misalignment of the lesion centers on CE-MRI and ultrasound was 3.9 ± 2.5 mm on the x-axis (mediolateral view), 3.6 ± 2.7 mm on the y-axis (anteroposterior view), and 4.3 ± 2.6 mm on the z-axis (craniocaudal view). No lesion had a misalignment greater than 10 mm on any of three axes. The accuracy of volume navigation was independent of patient age and the lesion size, location, and histopathologic findings (p > 0.05). Intermediate lesions, which had a depth of center of 11-20 mm on ultrasound had a mean misalignment of 2.6 ± 1.9 mm, compared with 5.5 ± 2.2 mm for deep lesions, which had a depth of center greater than 20 mm (p = 0.049). CONCLUSION: The volume navigation technique is an accurate method for coregistration of CE-MRI and sonographic images, enabling lesion localization within a limited volume.

Outcomes of unconventional utilization of BI-RADS category 3 assessment at opportunistic screening.

Background An important difficulty regarding the Breast Imaging Reporting and Data System (BI-RADS) category 3 assessment is the need for extensive diagnostic workup and an additional 6-month follow-up study. Purpose To evaluate the feasibility of the BI-RADS category 3 assessments at opportunistic screening. Material and Methods Mammography charts of 9062 screening patients in a major teaching hospital situated in an urban setting of a developing country were evaluated retrospectively (1997-2010). BI-RADS category 3 patients, called for a 6-month follow-up, which comprised a single-view spot or magnification mammogram. The length of follow-up period, compliance to periodic mammographic surveillance, cancer detection rate, and negative predictive values of category 3 assessments were calculated. Results Of the screened population, 9.2% were assigned BI-RADS category 3, and 31.2% of these cases were lost to follow-up. The mean follow-up period for 606 patients was 36.9 months. The negative predictive values for 6-month, 12-month, and final control studies were 90.9%, 87.5%, and 100%, respectively. Patient compliance for 6 months, 12 months, and any control evaluations beyond 12 months was low (50.0%, 29.8%, and 47.5%, respectively). Cancer detection rate was 0.8%. Conclusion Results of the study supports the feasibility of the BI-RADS category 3 assessments at opportunistic screening without any additional diagnostic workup. The practice of category 3 assessment following screening mammograms may be a more cost-effective method for developing countries with high recall rates and low resources in eliminating the maximum risk with minimum cost within the limits of available resources.

Impact of cyclooxygenase-2 over-expression on the prognosis of breast cancer patients.

OBJECTIVE: The aim of this present study was to assess the impact of COX-2 over-expression on breast cancer survival. MATERIAL AND METHODS: Non-metastatic invasive breast cancer patients who received adequate loco-regional and systemic treatments were evaluated. Patients' demographic, clinical, pathologic, and treatment-related and survival data were retrieved from their hospital files. COX-2, estrogen/progesterone receptor (ER/PR), HER-2/neu expression and Ki67 index of the tumors were determined immunohistochemically. As the primary objective, COX-2 positive and negative patients were compared in terms of overall (OS), disease-free (DFS) and breast cancer-specific survival (BCSS). Secondary objectives were to assess the independent prognostic factors for survival. In addition, the correlation of COX-2 expression with conventional prognostic and predictive factors of breast cancer was assessed. RESULTS: Two hundred and seventeen patients who underwent adequate breast cancer treatment between November 2004 and December 2013 were included in the study. The median follow-up was 37 months (range: 5-107). Eighty-one (37%) patients were COX-2 positive. OS, DFS, and BCSS were similar in COX-2 positive and negative patients. Ki67 index and age were significantly correlated with COX-2 expression (r=-0.116; p=0.02; r=0.159; p=0.02). PR expression was found to be the only independent factor for predicting OS, tumor size and molecular subtype classification were found to be the only independent factors for predicting DFS, and PR expression was found to be the only independent factor for predicting BCSS. CONCLUSION: Among the independent predictive and prognostic factors of breast cancer, COX-2 over-expression was only correlated with Ki67 index and age.

p95-HER2 and trastuzumab resistance in metastatic breast cancer; is immunohistochemistry appropriate?

PURPOSE: Unraveling the mechanisms underlying the resistance to trastuzumab is important for amending the prognosis of patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Experimentally, it has been shown that p95-HER2 positive breast tumors are resistant to trastuzumab. The aim of this study was to investigate the predictive and prognostic importance of p95-HER2 expression by immunohistochemistry in HER2-positive metastatic breast cancer patients treated with trastuzumab. METHODS: Only patients who had a histological diagnosis of HER2-positive metastatic breast cancer and who had received first line therapy containing trastuzumab were enrolled in the study. Immunohistochemistry was used to analyze p95-HER2 expression in the tissue blocks of the patients. RESULTS: The study was performed on 38 patients aged between 30 and 84 years. In 14 patients (36.8%), p95-HER2 was positive, whereas it was negative in the remaining 24 patients (63.2%). There was no significant correlation between p95-HER2 expression and overall survival, response to trastuzumab, and progression-free survival (PFS). CONCLUSION: Unlike previous reports, there was no correlation between the p95-HER2 expression and resistance to trastuzumab. It may be argued that an analysis using immunohistochemistry is inadequate for determining p95- HER2. In order to ascertain whether immunohistochemistry is an appropriate method, studies with larger patient groups are needed.

PTEN loss is not associated with trastuzumab resistance in metastatic breast cancer.

PURPOSE: Although the clinical benefits of trastuzumab are well known, intrinsic or acquired resistance is a commonly encountered clinical condition. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensine homologue (PTEN). This study investigated the relationship between trastuzumab response and loss of PTEN in metastatic breast cancer patients. METHODS: Patients with histologically confirmed human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer, who were treated with trastuzumab were enrolled into the study. PTEN expression was immunohistochemically evaluated. RESULTS: The patient median age was 50 years. Of 38 patients, 6 (15.8%) showed PTEN loss. No statistically significant difference was found between trastuzumab response, overall survival (OS) and progression-free survival (PFS) and PTEN loss (p=0.538). CONCLUSION: The activation of phosphatidylinositol 3-kinase (PI3K) pathway resulting from PTEN loss was not found to be correlated with trastuzumab response and survival. PTEN loss should not lead to exclusion of patients from the potential to benefit from trastuzumab administration.

Role of tyrosine kinase inhibition with imatinib in an encapsulating peritoneal sclerosis rat model.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model. METHODS: We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0-3 followed by a peritoneal rest period between weeks 3-6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0-3 followed by 50 mg/kg imatinib mesylate through weeks 3-6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-ß1 (TGF-ß1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry. RESULTS: An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-ß1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-ß1-positivity on immunohistochemistry between the groups. CONCLUSIONS: Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.

Linear Regression Modeling Based Scoring System to Reduce Benign Breast Biopsies Using Multi-parametric US with Color Doppler and SWE.

RATIONALE AND OBJECTIVES: To develop a simple ultrasound (US) based scoring system to reduce benign breast biopsies. MATERIALS AND METHODS: Women with BI-RADS 4 or 5 breast lesions underwent shear-wave elastography (SWE) imaging before biopsy. Standard US and color Doppler US (CDUS) parameters were recorded, and the size ratio (SzR=longest/shortest diameter) was calculated. Measured/calculated SWE parameters were minimum (SWVMin) and maximum (SWVMax) shear velocity, velocity heterogeneity (SWVH=SWVMax-SWVMin), velocity ratio (SWVR=SWVMin/SWVMax), and normalized SWVR (SWVRn=(SWVMax-SWVMin)/SWVMin). Linear regression analysis was performed by converting continuous parameters into categorical corresponding equivalents using decision tree analyses. Linear regression models were fitted using stepwise regression analysis and optimal coefficients for the predictors in the models were determined. A scoring model was devised from the results and validated using a different data set from another center consisting of 187 cases with BI-RADS 3, 4, and 5 lesions. RESULTS: A total of 418 lesions (238 benign, 180 malignant) were analyzed. US and CDUS parameters exhibited poor (AUC=0.592-0.696), SWE parameters exhibited poor-good (AUC=0.607-0.816) diagnostic performance in benign/malignant discrimination. Linear regression models of US+CDUS and US+SWE parameters revealed an AUC of 0.819 and 0.882, respectively. The developed scoring system could have avoided biopsy in 37.8% of benign lesions while missing 1.1% of malignant lesions. The scoring system was validated with a 100% NPV rate with a specificity of 74.6%. CONCLUSION: The linear regression model using US+SWE parameters performed better than any single parameter alone. The developed scoring method could lead to a significant decrease in benign biopsies.

Collapsing Glomerulopathy in a Patient with a TRPC6 Mutation Presenting as Rapidly Progressive Glomerulonephritis: A Case Report and Review of the Literature.

Collapsing glomerulopathy (CG) is a proliferative disease characterized by segmental or global wrinkling of the glomerular basement membrane and the formation of pseudocrescents, whereas focal segmental glomerulosclerosis (FSGS) is characterized by podocytopenia, and focal and segmental sclerosis of the glomeruli. Mutations in NPHS1, NPHS2, WT1, PLCE1, CD2AP, ACTN4, and TRPC6 have been reported in steroid-resistant FSGS patients. The mutations p.R895C and p.R895L in Exon 13 are the only ones in TRPC6 causing CG reported to date. Here, we present the case of a 17-year-old male patient with a collapsing variant of familial FSGS caused by a mutation in TRPC6 (p.R895C) who presented with rapidly progressive (crescentic) and proliferative glomerulonephritis.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2- Breast Cancer Patients.

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting "satisfactory response (SR)" to neoadjuvant chemotherapy (NAC) in HR+/HER2- breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T1-4, N0-2, M0 HR+/HER2- BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0-1) and no SR (RCB 2-3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN0 and ypN0i+) and no SR (ypNmic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either "no" or "low." In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2- BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2- BC patients.

Relationship of PPARG overexpression with prognostic parameters in papillary thyroid carcinoma.

Objectives: PAX8/PPARG chromosomal rearrangement is frequently seen in thyroid cancer, and PPARG overexpression has been shown in the follicular variant of papillary thyroid carcinoma, but not in papillary thyroid carcinoma other than the follicular variant. The main aim of this study was to investigate the frequency of PPARG overexpression among papillary thyroid carcinoma and if there were any variants of papillary thyroid carcinoma with PPARG overexpression other than the follicular variant. Methods: Immunohistochemical analysis of PPARG overexpression was performed using a PPARG monoclonal antibody in a series of 111 paraffin-embedded blocks of thyroid tumours. Of the patients in our study, 100 were diagnosed with papillary thyroid carcinoma, 9 with follicular adenoma and 2 with follicular carcinoma. Results: PPARG staining was detected in 19 of the 111 cases. Sixteen patients with PPARG overexpression had papillary thyroid carcinoma and 3 had follicular adenoma. Conclusion: PPARG overexpression was detected mainly in follicular-variant papillary thyroid carcinoma. Vascular invasion, lymphatic invasion, thyroid capsule invasion and lymph node positivity were lower in patients with PPARG overexpression.