Search

PurposeThe cost-effectiveness of BRCA1/2 screening for all newly diagnosed breast cancer remains controversial with respect to standard treatment. Further evidences that include incidence and outcome of BRCA1/2 pathogenic variants (PV) screened based on age or family history (FH) are needed to fully justify this conclusion. We aimed to investigate germline and tumor BRCA1/2 PV based on age screening in Chinese triple-negative breast cancer (TNBC) patients. MethodsPaired blood and tumor DNA from 124 unselected Chinese TNBC patients with less than or equal to 55 years were collected and analyzed for BRCA1/2 PV. Clinicopathological characteristics including age at diagnosis, FH and follow-up data were collected for further analysis. ResultsThe entire frequency of germline and tumor BRCA1/2 PV was 21.0% and 25%, respectively. Among them, 20 (16.1%) germline and 5 (4.0%) somatic BRCA1/2 single-nucleotide variant/insertion/deletions were found by NGS testing, 6 (4.8%) BRCA1 large genomic rearrangements were detected in blood DNA by MPLA. There was significant correlation between FH and germline BRCA1/2 PV among these patients. Patients with tumor BRCA1/2 mutations had significant improvements than non-carriers in PFS ( p =0.047). No significant impacts were found between various mutation status in OS outcomes. No significant differences were found between BRCA1 or BRCA2 and non-carriers in PFS or OS. ConclusionThere is a high incidence of germline and tumor BRCA1/2 PVs in Chinese TNBC patients with less than or equal to 55 years old. Tumor BRCA1/2 PV carriers showed an improved survival outcome. Our results suggest that BRCA1/2 PVs testing addressed within each specific clinical scenario could be more cost-effective for patients.

Objective The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy was evaluated. Results Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA–RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions Our study revealed the distinct molecular profile of thyroid tumors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

Ewing sarcoma (ES) is a highly malignant tumor that rarely occurs in the uterine cervix. Herein, we report 8 cases with ES arising primarily in the uterine cervix by focusing on clinicopathologic and molecular cytogenetic features and differential diagnoses. Eight cases of cervical ES were diagnosed between February, 2012, and September, 2018. The age of patients ranged from 13 to 47 years. Abnormal vaginal bleeding and lower abdominal pain were the most common symptoms. Histologically, the tumor was composed of uniform, round, and oval cells with a narrow rim of eosinophilic cytoplasm. Fibrous septa were observed between tumor cell nests. The tumors showed brisk mitotic activity and areas of coagulative necrosis. According to immunohistochemical studies, 50% (4/8) of the cases were positive for cytokeratin (AE1/AE3), and 87.5% (7/8) were positive for synaptophysin, which resulted in a diagnostic confusion with small cell carcinoma, primarily when dealing with small cervical biopsies. Molecular testing demonstrated the rearrangement of the EWSR1 gene in all of the 8 cases, which confirmed the diagnosis of ES. Although rare, ES should be considered as indicators of cervical small round cell neoplasms. Molecular analysis may greatly contribute to the final diagnosis of ES occurring in this unusual location.

Total omentectomy is often performed with gastrectomy as radical surgery for gastric cancer (GC) patients. However, it remains controversial whether GC patients can benefit from omentectomy. The aim of this study was to analyze the incidence and clinical significance of tumor deposits (TDs) in different anatomical subregions of perigastric omentum in GC patients undergoing gastrectomy with total omentectomy.From October 2011 to December 2013, 1253 patients who underwent gastrectomy with total omentectomy for GC were retrospective reviewed. The TDs in different anatomical subregions of perigastric omentum were examined.Of 1253 patients, TDs positivity was 11.2%. Tumor deposits in the omentum of greater curvature and in the omentum of lesser curvature were associated with lymphovascular invasion, perineural invasion, advanced tumor node metastasis stages, and unfavorable survival. Besides, TDs in the proximal omentum of greater curvature and in the omentum of lesser curvature correlated with older patients and larger tumors. Kaplan-Meier curves showed that patients with TDs had worser overall survival (OS) than those without, regardless of TD positions. Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. Tumor deposits in the proximal omentum of greater curvature was an independent prognostic factor for OS. Moreover, only patients classified as pT4 had TDs in the distal omentum of greater curvature.Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. In addition, partial omentectomy might be practicable for gastric cancer patients classified as T3 or shallower tumors.

Background Radiogenomics explores the association between imaging features and genomic assays to uncover relevant prognostic features; however, the prognostic implications of the derived signatures remain unclear. Purpose To identify preoperative radiogenomic signatures of estrogen receptor-positive breast cancer associated with the Oncotype DX recurrence score (RS) and to evaluate whether they are biomarkers for survival and responses to neoadjuvant chemotherapy (NACT). Materials and Methods In this retrospective multicohort study, three data sets were analyzed. The radiogenomic development data set, with preoperative dynamic contrast-enhanced MRI and RS data obtained between January 2016 and October 2019 was used to identify radiogenomic signatures. Prognostic implications of the imaging signatures were assessed by measuring overall survival and recurrence-free survival in the prognostic assessment data set using a multivariable Cox proportional hazards model. The therapeutic implication of the radiogenomic signatures was evaluated by determining their ability to predict the response to NACT using the treatment assessment data set obtained between August 2015 and March 2019. Prediction performance was estimated by using the area under the receiver operating characteristic curve (AUC). Results The final cohorts included a radiogenomic development data set with 130 women (mean age, 52 years ± 10 [standard deviation]), a prognostic assessment data set with 116 women (mean age, 48 years ± 9), and a treatment assessment data set with 135 women (mean age, 50 years ± 11). Radiogenomic signatures (n = 11) of texture and morphologic and statistical features were identified to generate the predicted RS (R2 = 0.33, P < .001). A predicted RS greater than 29.9 was associated with poor overall and recurrence-free survival (P = .001 and P = .007, respectively); predicted RS was greater in women with a good NACT response (30.51 ± 6.92 vs 27.35 ± 4.04 [responders vs nonresponders], P = .001). By combining the predicted RS and complementary features, the model achieved improved performance in prediction of the NACT response (AUC, 0.85; P < .001). Conclusion Radiogenomic signatures associated with genomic assays provide markers of prognosis and treatment in estrogen receptor-positive breast cancer. © RSNA, 2021 Online supplemental material is available for this article.

We report 10 additional cases of GLI1-altered mesenchymal tumor to further delineate its clinicopathological and molecular spectrum. There were seven males and three females with a median age of 31 years (range 1.3 ~ 75 years). Five tumors arose in the oral cavity, one each in the stomach, uterine cervix, elbow, groin, and thigh. Histologically, all cases except one were composed of monomorphic round to epithelioid cells showing an infiltrative multinodular growth pattern. The neoplastic cells were surrounded by a rich network of capillary vessels. Vessel invasion or subendothelial protrusion into the vascular space was commonly present. One tumor developed regional lymph node metastasis. The remaining case showed a predominantly spindle cell tumor. By immunohistochemistry, most tumors showed diffuse staining of CD56 (8/8) with variable expression of S100 protein (7/8). In three tumors harboring amplified genes, strong and diffuse nuclear staining of MDM2 (2/3) and CDK4 (3/3) were noted. Next-generation sequencing (NGS) studies revealed GLI1 fusions in 7 cases and GLI1 amplification in 2 cases, which were validated by fluorescence in situ hybridization (FISH) analysis in the majority of cases. One case did not show fusion gene by RNA-seq, but FISH revealed both amplification and break-apart of GLI1 gene. Follow-up information showed local recurrences in two patients. All other patients remained disease-free at the last follow-up. Our study further demonstrates that mesenchymal tumors with GLI1 alterations represent a distinctive clinicopathological entity. Although the tumor has a propensity for the tongue, it can also arise in somatic soft tissues as well as in visceral organs. Based on the characteristic morphological features and genomic profiles, we propose the term “GLI1-altered mesenchymal tumor” to describe this emerging entity.

Background: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with HER2 IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods: 195 HER2 FISH-equivocal breast cancers were collected between 2014 and 2018. The molecular subtype was determined according to 2013 St Gallen consensus, and HER2 status was also redefined following 2018 ASCO/CAP guideline. All cases were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results: 183 (93.8%) of 195 FISH-equivocal cases were of luminal subtype, while the other 12 (6.2%) were undetermined. Using 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized to HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) cases were treated with trastuzumab, but showed no difference in prognosis with patients who didn’t receive targeted therapy.Conclusions: In this study, all HER2 FISH-equivocal breast cancers were reclassified to be HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

Oncotype DX recurrence score (RS) is increasingly used to differentiate patients at high risk of recurrence from those who have low risk of recurrence. Despite the promising value, this genetic technology has disadvantage in its expensive and currently not readily available in most of the institute, which limited the clinical applications in management of breast cancer. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is becoming standard-of-care in breast cancer management. It is of vital importance to predict Oncotype DX RS using radiomics from DCE-MRI to perform a noninvasive evaluation of recurrence in breast cancer. To this end, 131 patients were included in the dataset, of which 13 (9.9%) had a low risk of recurrence (RS

BACKGROUND: Discrepancies in genetic alterations found in melanoma are conspicuous between different ethnic groups. With the approval of BRAF- and MEK-targeted inhibitors in China, it is necessary to further elucidate the landscape of gene mutation in Chinese melanoma patients. METHODS: The frequency and distribution of BRAF, C-KIT, and NRAS mutations in 691 melanoma patients was determined, and the statistical significance of correlations between different gene mutations and clinicopathological features was analyzed. RESULTS: Among a total of 691 patients, BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (145/166, 87.3%). Statistical analyses showed that younger patients (

Introduction: Lung cancer is the leading cause of cancer-related morbidity and mortality in the People’s Republic of China. Targeted therapies for patients with lung cancer, which depend on accurate identification of actionable genomic alteration, have improved survival compared with previously available treatments. However, data on the types of molecular testing often used in the People’s Republic of China, and how they have changed over time, are scarce. We explored the overall landscape of molecular testing of lung cancer in mainland People’s Republic of China in the past decade. Methods: We distributed a stratified random sampling survey of molecular testing to 49 hospitals from members of the Molecular Pathology Collaboration Group of Chinese Anti-Cancer Association which was weighted by the numbers of lung cancer cases in seven different geographic regions in mainland People’s Republic of China from 2010 to 2019. The questionnaire contained four parts for all respondents. The questionnaire ascertained the use of approved in vitro diagnostic (IVD) devices published by the Center for Medical Device Evaluation, National Medical Products Administration of the People’s Republic of China. Results: A total of 226,227 NSCLC specimens were tested from 2010 to 2019 in the selected hospitals. The annual number of initiated molecular tests increased over time (p < 0.0001), with an average annual growth rate of 31.8%. A notable increase in the number of molecular tests occurred during 2014 and 2016, which coincided with the approval of the National Medical Products Administration to IVD devices. For the diagnosis of molecular subtypes, EGFR mutation testing was first conducted in year 2007, followed by ALK translocation testing in 2010 and ROS1 in 2011. For other rare genetic variations in NSCLC, BRAF mutation testing was first launched in 2012, MET exon 14 skipping mutation in 2014, HER2 exon 20 mutations in 2017, and RET translocation in 2015. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east People’s Republic of China (34.7%, 17 of 49) and the smallest number located in northwest People’s Republic of China (6.1%, 3 of 49). The growth trends we observed illustrate the progress and increasing capability of molecular testing of lung cancer achieved in mainland People’s Republic of China in the decade from 2010. Conclusions: In the decade 2010 to 2019, progress and increased capability of molecular testing of lung cancer were achieved in mainland People’s Republic of China. Further efforts should address the clinical application of next-generation sequencing technology, rare genomic aberrations, and the balance between novel genomic testing techniques and the approval of IVD products.

Background: Little is known about the morphological and molecular features of intra-thoracic myoepithelial tumors. Here, we describe a rare pulmonary myoepithelial tumor with novel TRPS1-PLAG1 fusions.Case presentation: A 30-year-old male presented with multiple lung nodules that detected by routine computed tomography (CT) scan 3 years ago. Positron emission tomography-computed tomography (PET-CT) demonstrated a well-circumscribed mass with a diameter of 3cm in the left pulmonary hilum and multiple nodules in bilateral lungs. No other extra-thoracic primary lesion and distant metastasis was found. The clinical history was not other specified. Microscopically, these lesions were well-defined, showed nodular growth pattern filling the bronchioles and alveoli. The tumor cells were epithelioid to plasmacytoid with slightly eosinophilic cytoplasm, arranged in aggregates, nests and cords. Myxoid background presented in some foci. Nuclear pleomorphism was mild and mitotic activity was not prominent. No distinct gland formation was identified. Immunostains demonstrated that the tumor cells were diffusely positive for pan-cytokeratin (AE1/AE3), CK5/6, S100, SOX10, and negative for calponin. Noticeably, a TRPS1-PLAG1 gene fusion was identified in this tumor by targeted RNA sequencing involved TRPS1 exon1 and PLAG1 exon2, this rare rearrangement was validated by fluorescence in situ hybridization (FISH) for PLAG1 break-apart probe, and 30% tumor cells showed break apart signals. Conclusions: Here we present the first case of a disseminated thoracic myoepithelial tumor with novel TRPS1-PLAG1 fusions. Targeted RNA sequencing strongly facilitates precise classification and providing opportunities for unknown fusion partner discovery, which is significant for risk stratification and development of potential therapeutic targets.

To identify triple-negative (TN) breast cancer imaging biomarkers in comparison to other molecular subtypes using multiparametric MR imaging maps and whole-tumor histogram analysis. This retrospective study included 134 patients with invasive ductal carcinoma. Whole-tumor histogram-based texture features were extracted from a quantitative ADC map and DCE semi-quantitative maps (washin and washout). Univariate analysis using the Student’s t test or Mann–Whitney U test was performed to identify significant variables for differentiating TN cancer from other subtypes. The ROC curves were generated based on the significant variables identified from the univariate analysis. The AUC, sensitivity, and specificity for subtype differentiation were reported. The significant parameters on the univariate analysis achieved an AUC of 0.710 (95% confidence interval [CI] 0.562, 0.858) with a sensitivity of 63.6% and a specificity of 73.1% at the best cutoff point for differentiating TN cancers from Luminal A cancers. An AUC of 0.763 (95% CI 0.608, 0.917) with a sensitivity of 86.4% and a specificity of 72.2% was achieved for differentiating TN cancers from human epidermal growth factor receptor 2 (HER2) positive cancers. Also, an AUC of 0.683 (95% CI 0.556, 0.809) with a sensitivity of 54.5% and a specificity of 83.9% was achieved for differentiating TN cancers from non-TN cancers. There was no significant feature on the univariate analysis for TN cancers versus Luminal B cancers. Whole-tumor histogram-based imaging features derived from ADC, along with washin and washout maps, provide a non-invasive analytical approach for discriminating TN cancers from other subtypes. • Whole-tumor histogram-based features on MR multiparametric maps can help to assess biological characterization of breast cancer. • Histogram-based texture analysis may predict the molecular subtypes of breast cancer. • Combined DWI and DCE evaluation helps to identify triple-negative breast cancer.

Gastric cancer (GC) is one of the most common cancers and is the second-leading cause of cancer-associated morbidity worldwide. Oxysterols are oxidized derivatives of cholesterol that may be important in many biological processes, but the levels and roles of oxysterols in gastric tumours remain to be elucidated. The levels of cholesterol, oxysterols and sulfated oxysterols in human gastric tumour tissues, adjacent normal mucosal tissues, cancerous gastric juice and gastric juice obtained from healthy subjects were detected by LC-MS. It was found that the levels of 24(R/S),25-EC and 27HC in human gastric tumour tissues and cancerous gastric juice were significantly increased compared with those of adjacent normal mucosal tissues and gastric juice from healthy subjects. Compared with normal gastric mucosal tissue, the levels of sulfated 25-hydroxycholesterol (25HC3S) and the ratio of 25HC3S/25HC were decreased in human gastric tumour tissues, which might be related to the dramatically decreased SULT2A1 expression in gastric tumour tissue. Both 24(R/S),25-EC and 27HC suppressed gastric cancer proliferation, which was not altered by LXRα-siRNA treatment. The suppression of cell proliferation induced by 27HC was attenuated by LXRβ-siRNA, but the suppression of cell proliferation induced by 24(R/S),25-EC was intensified by LXRβ-siRNA. Both 24(R/S),25-EC and 27HC dramatically inhibited HGC-27 cell migration, which was attenuated by the co-transfection of cells with LXRα-siRNA and LXRβ-siRNA, but not LXRα-siRNA or LXRβ-siRNA alone. In conclusion, the accumulated 24(R/S),25-EC and 27HC in human gastric tumour tissues might play important roles in gastric cancer development.

Aims Secretory breast carcinoma is a rare, low-grade, translocation-associated invasive carcinoma with unique morphology and excellent prognosis. Three patterns (microcystic, tubular, solid) have often been described in secretory carcinoma. Herein, we reported one case of secretory breast carcinoma with an uncommon papillary-predominant growth pattern. Methods and results The patient was a 53-year-old female with a mass located in outer upper quadrant of her right breast. The patient had one positive axillary lymph node. Morphologically, tumour cells were arranged in a papillary growth pattern with sclerosis in most areas; glandular and microcystic patterns were observed only in focal areas at the periphery. The presence of intracellular and extracellular secretory material was observed. Tumour cells were mild-to-moderately atypical with granular eosinophilic to foamy cytoplasm. Tumour cells were triple-negative [negative for oestrogen receptor (ER), progestogen receptor (PR) and human epidermal growth factor receptor 2 (HER2)] with a basal-like phenotype, and strongly positive for S-100 protein. P63 and calponin staining showed the absence of myoepithelial cells around tumour cells. Fluorescence in-situ hybridization (FISH) analysis showed ETS variant 6 (ETV6) gene rearrangement. Conclusions Our study indicated that besides typical growth patterns (microcystic, solid and tubular), secretory carcinoma could also present with a papillary-predominant architecture. These cases should be differentiated from other breast tumours with a papillary pattern. It may have clinical significance to recognize this uncommon morphology variant of secretory carcinoma in routine practice.

Either modulated illumination or temporal fluctuation analysis can assist super-resolution techniques in overcoming the diffraction limit of conventional optical microscopy. As they are not contradictory to each other, an effective combination of spatial and temporal super-resolution mechanisms would further improve the resolution of fluorescent images. Here, a super-resolution imaging method called fluctuation-enhanced Airyscan technology (FEAST) is proposed, which achieves ~40 nm lateral imaging resolution and is useful for a range of fluorescent proteins and organic dyes. It was demonstrated not only to obtain different subcellular super-resolution images, but also to improve the accuracy of counting the average human epidermal growth factor receptor 2 (HER2) copy number for diagnosis in breast cancer. Furthermore, the combination of FEAST and sample expansion microscopy (Ex-FEAST) improves the lateral resolution to ~26 nm.

Context.— The updated American Society of Clinical Oncology/College of American Pathologists guideline for human epidermal growth factor receptor 2 (HER2) testing in breast cancer requires pathologists to re-evaluate HER2 status. Objective.— To define HER2 status of breast cancer using immunohistochemistry and fluorescence in situ hybridization. Design.— Diagnostic reports of invasive breast cancers made between 2014 and 2018 with HER2 immunohistochemistry and fluorescence in situ hybridization results were retrieved. HER2 status was re-defined using the updated recommendations. Results.— Of 2514 tumors, 89.7% (2254 of 2514) suggested for fluorescence in situ hybridization assay were HER2 immunohistochemistry 2+. Approximately 8.9% (225 of 2514) and 1.4% (35 of 2514) of tumors were of immunohistochemistry 0/1+ and 3+, respectively. Based on the average HER2 copy number and HER2:CEP17 ratio, tumors were assigned into 5 groups, including 13.1% (330 of 2514) group 1 tumors, 2.1% (52 of 2514) group 2 tumors, 1.1% (27 of 2514) group 3 tumors, 7.0% (175 of 2514) group 4 tumors, and 76.8% (1930 of 2514) group 5 tumors. In combination with immunohistochemistry, all tumors in group 2 and group 4 changed HER2 status, from positive and equivocal into negative, respectively, while group 3 tumors remained positive. Comparative analyses of clinicopathologic features of tumors in different groups revealed that group 2 and 4 tumors displayed worse clinicopathologic features than those of group 5, while group 3 tumors shared similar clinicopathologic features to those of group 1. Conclusions.— Following the updated guideline, HER2 status is clearly designated. Significant differences regarding clinical features were observed between tumors in different groups but they share the same HER2 status, suggesting further validation of the accuracy of this diagnostic approach is warranted.

Purpose The aim of this study was to investigate whether whole-lesion histogram and texture analysis using apparent diffusion coefficient can discriminate between idiopathic granulomatous mastitis (IGM) and invasive breast carcinoma (IBC), both of which appeared as non-mass enhancement lesions without rim-enhanced masses. Method This retrospective study included 58 pathology-proven female patients at two independent study sites (27 IGM patients and 31 IBC patients). Diffusion-weighted imaging (3b values, 50, 400 or 500, and 800 s/mm2) was performed using 1.5 T or 3 T MR scanners from the same vendor. Whole-lesions were segmented and 11 features were extracted. Univariate analysis and multivariate logistic regression analysis were performed to identify significant variables for differentiating IGM from IBC. Receiver operating characteristic curve was assessed. The interobserver reliability between two observers for the histogram and texture measurement was also reported. Results The 5th percentile, difference entropy and entropy of apparent diffusion coefficient showed significant differences between the two groups. An area under the curve of 0.778 (95 % CI: 0.648, 0.908), accuracy of 79.3 %, and sensitivity of 87.1 % was achieved using these three significant features. No significant feature was found with the multivariate analysis. For the interobserver reliability, all apparent diffusion coefficient parameters except skewness and kurtosis indicated good or excellent agreement, while these two features showed moderate agreement. Conclusions Whole-lesion histogram and texture analysis using apparent diffusion coefficient provide a non-invasive analytical approach to the differentiation between IGM and IBC, both presenting with non-mass enhancement without rim-enhanced masses.

Invasive micropapillary carcinoma is characterized by the inside-out growth of tumor clusters and displays incomplete membrane immunostaining of HER2. According to the 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2-testing recommendation, moderate to intense but incomplete staining could be scored as immunohistochemical 2+. Furthermore, the criteria of immunohistochemical 3+ for this staining pattern are not mentioned. One hundred and forty-seven cases of invasive micropapillary carcinoma with moderate-to-intense HER2 immunostaining were enrolled. Invasive micropapillary carcinoma components of all cases were scored as immunohistochemical 2+ based on the 2018 ASCO/CAP recommendation. The invasive micropapillary carcinoma component varied from 10% to 100% (mean, 80%). Invasive micropapillary carcinoma components of all 147 tumors exhibited reversed polarity and incomplete basolateral HER2 membrane staining. One hundred and seventeen of the tumors (80%, 117/147) had moderate staining, and 38 (32%, 38/117) showed HER2 gene amplification by fluorescence in-situ hybridization. HER2 gene was amplified in all the remaining 30 tumors (20%, 30/147) that exhibited intense basolateral membrane staining. Besides, average HER2 signals per cell and ratio of HER2/CEP17 were significantly higher in the intense-staining tumors compared with the moderate-staining tumors (p

BACKGROUND: Studies on the prevalence of BRCA1/2 mutations in ovarian cancer mainly focused on germline single-nucleotide variant (SNV)/insertion/deletion (indel). The status of large genomic rearrangement (LRG) and somatic mutation were poorly investigated. METHODS: Paired blood and tumor DNA from an unselected cohort of 115 Chinese high grade serous ovarian cancer (HGSOC) patients were collected and analyzed for BRCA1/2 SNV and indel by NGS. BRCA1/2 LRG was detected by MLPA. Clinicopathological characteristics including age at diagnosis, FIGO stage, family history and follow-up data were collected for further analysis. RESULTS: A total of 115 HGSOC patients were screened. Among them, 30 (26.1%) had germline BRCA1/2 mutations, including 19 (16.5%) SNV/indels, 5 (4.3%) LGRs in BRCA1, and 6 (5.2%) SNV/indels in BRCA2. Ten (8.7%) had somatic BRCA1/2 mutations, including 5 (4.3%) in BRCA1 and 5 (4.3%) in BRCA2. The entire tumor BRCA1/2 mutation frequency was 34.8%. No patients were found with two or more deleterious BRCA1/2 mutations. The proportion of germline (66.7%) and tumor (75%) mutation carriers was significantly increased for patients with family history when compared with those without (P

AIMS To better understand the histogenesis, prognosis and feasible treatment of pancreatic carcinosarcoma, a rare type of neoplasia. METHODS AND RESULTS We investigated eight additional cases of pancreatic carcinosarcoma at a single institution, including the clinicopathological, immunohistochemical, and KRAS mutation characteristics. We have also reviewed the current literature on this rare type of neoplasia, and summarized the clinicopathological features and feasible treatments. As a result, concordant strong nuclear immunoreactivity for P53 protein and the same type of KRAS gene mutation, c.35G>A (p.G12D) or c.35G>T (p.G12V), were showed in both carcinomatous and sarcomatous components in five of eight cases. Furthermore, we found that the patients treated with surgery plus postoperative chemotherapy had longer survival than those treated with surgery only (P = 0.034 and P = 0.131 for overall survival and disease-free survival, respectively), although Cox regression multivariate analysis indicated that it was not an independent predictor. In addition, we found KRAS mutant allele-specific imbalance in four of our five cases of pancreatic carcinosarcoma, which was associated with advanced disease and a worse prognosis. CONCLUSIONS This is the largest panel of cases of pancreatic carcinosarcoma studied so far, including clinicopathological, immunohistochemical and molecular cytogenetic features. Our findings indicate that the tumour could have been of monoclonal origin, and that the sarcomatous components might have arisen from metaplastic transformation of the carcinomatous components. Our results also suggest that surgery plus POC including gemcitabine may be a good choice for patients with pancreatic carcinosarcoma.

The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30–40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP-2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation.

e13644 Background: Mismatch repair (MMR)/microsatellite instability (MSI) testing is recommended by NCCN Guidelines to screen for Lynch Syndrome as well as to predict response to immune checkpoint inhibitors in solid tumors. Conventional methods for MSI detection, immunohistochemistry (IHC) and polymerase chain reaction (PCR), often require non-tumor controls as well as a long turnaround time. The Idylla system, in contrast, is a fully automated quantitative PCR unit with a turnaround time of 2.5 hours. Neither does it require normal tissue or special training to operate. The Idylla MSI Test has been CE-marked for its reliability among Caucasian colorectal cancer (CRC) patients, but has never been validated in Chinese CRC population. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from 87 CRC patients and were subjected to MMR/MSI detection using IHC, PCR and the Idylla test separately. The Idylla MSI Test incorporates 7 novel MSI loci, ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, and SULF2. The sensitivity and specificity of the Idylla system were evaluated in comparison with PCR and IHC. Results: Of the 87 patients enrolled, both IHC and PCR identified 55 to be MMR-deficient (dMMR)/MSI-high (MSI-H), of which 4 were MSS using Idylla, and 32 to be MMR-proficient (pMMR)/microsatellite stable (MSS) where Idylla classified one as MSI-H, yielding a sensitivity of 92.7%, a specificity of 96.9% and an overall concordance of 94.3%. Re-examination of the 5 discordant cases (4 false negatives and 1 false positive) using DNA extractions instead of tissue slices on the Idylla platform displayed 100% consistency with IHC/PCR. Confirmation on the Idylla system using recut sections corrected 3 false negatives and 1 false positive, with all tumor contents of ≥20%, 1 Idylla-defined MSS sample with 5% tumor content remained discordant even after sample enrichment. Conclusions: The Idylla system provides a fast, reliable, and user-friendly solution to MSI detection in Chinese CRC patients with high sensitivity and specificity. Upfront assessment of tissue sample quality ( i.e. tumor area and tumor cell fraction) is critical for the accuracy of this test. The reproducibility of the assay warrants further investigation.

Additional file 1: Figure S1. The TIC of the samples. Figure S2. The expression of SULT2B1 in human gastric tumor. Table S1. MRM condition, quantitation ranges and linearity data of the samples. Table S2. LOD and LOQ data of the samples. Table S3. Primer sets used for qRT-PCR.

Aims To better understand the tumourogenesis and molecular features of hepatic carcinosarcoma (HCS). Methods and results We selected 13 cases of HCS, including the clinicopathological and immunohistochemical features, and analysed the molecular alterations in separately microdissected carcinomatous and sarcomatous components in eight cases by using targeted next-generation sequencing with a panel of 329 cancer-related genes. As a result, transitional areas were observed between the two components of HCS in all cases. Concordance and overlap in genetic alterations were identified in the two histological components of the eight HCS patients, indicating the clonal relatedness of the two tumour components. The most common gene alterations found in both components were TP53 (75%, 6/8) and NF1/2 (38%, 3/8) mutations and VEGFA amplification (25%, 2/8), which may be strongly associated with HCS tumorigenesis. Unique mutations and amplifications found only in one component were also identified. Amplifications involving MET (38%, n = 3/8) and PDGFRA (25%, n = 2/8) were present only in the sarcomatous components, whereas mutation affecting ERBB4 (25%, n = 2/8) and amplifications of CCND1 and FGF3/4/19 (38%, n = 3/8) were present only in the carcinomatous components, indicating their involvement in the clonal evolution of HCS. Furthermore, multiple potential therapeutic targets were identified for HCS. Conclusions Our findings indicate that HCS could have been of monoclonal origin, and that the diverse clonal evolution might be driven by special molecular alterations in each tumour component. Our results also identify multiple therapeutic targets of HCS, which are valuable for the personalised treatment of HCS.

AIMS The protein expression of programmed death-ligand 1 (PD-L1) has been recognised as being a biomarker for poor prognosis in diffuse large B-cell lymphoma (DLBCL). The aims of this study were to determine PD-L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL. METHODS AND RESULTS In this study, we used fluorescence in-situ hybridisation, RNA in-situ hybridisation and immunohistochemistry to determine PD-L1 status at three different levels in 287 DLBCL samples with follow-up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD-L1 DNA amplification, 19.9% (57/287) had high PD-L1 mRNA expression, and 11.8% (34/287) had high PD-L1 protein expression. Both mRNA and protein expression of PD-L1 were significantly higher in non-germinal centre B-cell-like (GCB) DLBCL than in GCB DLBCL (P

Purpose To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone VE1) for specific detection of the BRAF V600E mutant protein in formalin-fixed paraffin-embedded papillary thyroid carcinoma (PTC) specimens. Methods A total of 118 PTC cases and 116 control cases processed between January 2008 and June 2010 were selected and created tissue microarrays (TMAs) for the study. BRAF V600E (VE1) IHC was performed on tissue sections from PTC cases to determine mutation status. Molecular tests (Sanger sequencing/ARMS) were used to confirm the BRAF V600E gene mutation in primary PTC. Results A uniformly cytoplasmic staining throughout the tumors was observed in IHC-positive cases. BRAF V600E was detected in 68.6% (81/118) of PTC samples by IHC and in 61.9% (73/118) by Sanger sequencing/ARMS. The overall concordance between IHC and Sanger sequencing/ARMS was 93.2% (110/118). The sensitivity and specificity of the BRAF V600E IHC was 100% (73/73) and 82.2% (37/45), respectively. Positive and negative predictive values were 90.1% (73/81) and 100% (37/37), respectively. Expression of the BRAF V600E mutant protein was detected in all of 59 cases of primary carcinoma and corresponding metastatic carcinoma in lymph nodes. The concordance between IHC staining in primary and metastatic PTC was 100% (59/59). Conclusion IHC using VE1 antibody for detection of the BRAF V600E mutant protein expression in PTC showed high sensitivity and acceptable specificity, which are critical for diagnostic purposes. IHC staining for BRAF V600E showed uniformly cytoplasmic expression in both primary tumor and metastatic nodes. Therefore, IHC has high practical value for the detection of the BRAF V600E mutation in metastatic and primary PTC.

This study was retrospectively performed to analyze correlations between clinicopathological features of colorectal cancer (CRC) and mutations in KRAS, NRAS, and BRAF in Chinese patients, and to assess the importance of detecting additional mutations in KRAS exons 3 and 4 and NRAS in patients with CRC. RAS (KRAS and NRAS) and BRAF mutations were detected in 715 and 655 patients respectively. The mutation rate of RAS (KRAS or NRAS) was 45.6% (326/715). KRAS exon 2 mutations were evaluated in 36.6% of patients (262/715). Additional mutations in RAS exons occurred in 9.0% of patients (64/715), including KRAS exons 3 and 4 in 5.6% (40/715) and NRAS exons 2, 3, or 4 in 3.4% (24/715). Among 453 patients with wild-type KRAS exon 2, 14.1% (64/453) had other mutations in RAS exons. The most frequent sites of mutations were codons 12, 13, 61, and 146 in KRAS and codons 12 and 61 in NRAS. The mutation rate of BRAF (exon 15) was 4.0% (26/655), and the most frequent mutation site was codon 600. Among 440 patients with CRC who had a primary tumor resection at our center, those with mucinous or signet ring cell CRC were more likely to harbor KRAS mutations than those with adenocarcinoma (62.7% vs. 43.6%, P=0.006 and 59.3% vs. 39.6%, P=0.004, respectively). Female patients had a higher BRAF (exon 15) mutation rate than male patients (5.1% vs. 1.1%, P=0.017). Detection of both KRAS and NRAS mutations is useful for selecting patients who will benefit from anti-EGFR monoclonal antibody therapy. KRAS mutations were more frequent in patients with mucinous adenocarcinoma/signet ring cell CRC, whereas BRAF mutations were more common in female patients with CRC.