Purpose: The aim of this study is to investigate the genetic heterogeneity (carcinomatous vs. sarcomatous components) and predictive biomarkers in patients with pulmonary sarcomatoid carcinoma (PSC). Methods: Genetic alterations and biomarkers of immunotherapy were performed in a discovery set (n = 6) of PSC. Next-generation sequencing (NGS) on a pan-cancer gene panel was applied to detect the genetic alterations in each component, and the respective mutation profiling and tumor mutation burden (TMB) were compared as well. Immunohistochemistry (IHC) assay with SP263 antibody was used to detect the protein expression of programmed death-ligand 1 (PD-L1) in each component. Results: Comparative genetic analysis revealed that the separate carcinomatous and sarcomatous components shared strikingly common mutations. TP53 (4/6, 66.7%) was the most common genetic alteration in 6 PSC patients. MET exon 14 skipping was detected in one case, accounting for 16.7%. An EZR-ROS1 fusion (EZR: intron10-ROS1: intron32) was identified in one case. The TMB of the two components was similar. Nevertheless, significantly higher PD-L1 expression was found in carcinomatous components compared to sarcomatous components. MDM2 amplification was detected in 2/6 (33.3%) of cases and SIK11 mutation in 1/6 (16.7%) of cases. Conclusions: PSC containing carcinomatous and sarcomatous components had a mild heterogeneity; the two components may evolve from common ancestral cells. High PD-L1 expression suggests that immunotherapy could be used as a potential therapy for PSC patients, while patients with negative immune-responsive genes need to be screened out. Altogether, these findings further highlight that the detection of genetic alteration and PD-Ll expression plays an important role in treatment of patients with PSC. (C) 2020 Elsevier Inc. All rights reserved.

Background Sarcomatoid carcinoma (SaCa) of the palatine tonsil is a rare and aggressive subset of head and neck (H&N) cancer which is characterized by insensitivity to surgery and radiotherapy and a poor prognosis. Immunotherapy has led advances in the treatment of melanoma and H&N cancer, but the combined effects of immunotherapy and chemotherapy have not been sufficiently investigated. Case Presentation Herein, we report the case of 29-year-old Chinese women with local advanced non-resectable SaCa of the palatine tonsil who exhibited a substantial partial response to toripalimab and chemotherapy followed by radiation therapy. To the best of our knowledge, this is the first report of its successful application in this context. Conclusion Toripalimab combined with chemotherapy may be an effective approach for locally advanced H&N cancer in rare categories of patients, which was the first application as far as we know.

Background: Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous morphological components and immunophenotypical features intermingled within the same lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated MMFC. Methods: A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of calcitonin (Ctn; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/mL), and thyroglobulin (Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy, suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy, along with extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were performed. Results: The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A, and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation manifested in the patient but was not detected in other family members. Follow up showed that the serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16 months after the surgery. Conclusion: Particular and diverse patterns of MMFC should be recognized with immunostaining features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological behavior and the treatment is mostly radical surgery.

Platinum-based postoperative adjuvant chemotherapy is the standard treatment for stage II-IIIA non-small cell lung cancer (NSCLC). Novel therapeutic modalities are required to improve the outcome of an early stage NSCLC. Patients with advanced NSCLC having anaplastic lymphoma kinase (ALK) fusion protein are sensitive to ALK inhibitors such as crizotinib. This study aimed to further explore the clinicopathological characteristics of postoperative patients with early-stage lung cancer harboring ALK fusion protein and provide a basis to carry out postoperative adjuvant crizotinib treatment. A total of 19 patients were retrospectively reviewed, and the clinicopathological parameters and follow-up data were collected and analysed. ALK rearrangements easily exist in male and in non-smokers patients with adenocarcinoma histology. Brain metastasis occurs easily, and prognosis of patients with stage IIIA is relatively poor. Detection of ALK fusion protein should be a routine testing. Postoperative adjuvant crizotinib treatment for patients with stage IIIA NSCLC harboring ALK fusion protein is promising.

In this meta-analysis on correlation between schizophrenia and breast cancer (BC), we found that the incidence of schizophrenia is positively correlated with BC, and the incidence of BC in schizophrenia patients is increased in a certain degree. Because of the effects of potential bias and publication bias, the conclusion needs more high-quality studies to increase the strength of evidence. Purpose: To determine the correlation between schizophrenia and breast cancer (BC). Methods: We searched relevant articles indexed in the PubMed, Embase, and Cochrane Library databases; managed the data in Endnote X7 software; evaluated literature quality by Newcastle-Ottawa quality evaluation criteria; designed tables; and extracted relevant data. The main outcome measure was BC incidence. Effect values were risk ratio and 95% confidence intervals. We used Stata 13.1 software to perform the meta-analysis, choosing a corresponding combination model according to heterogeneity test results and carrying out subgroup analyses in order to better understand the stability of results through sensitivity analysis. Results: On the basis of 15 studies that assessed patients in different geographic regions, meta-analysis results showed that BC incidence between the exposure group (patients with schizophrenia) and the control group (nonschizophrenia population or general population) had statistical difference (risk ratio =1.18; 95% confidence interval, 1.05, 1.32), thus showing that BC incidence in patients with schizophrenia is higher than in the nonschizophrenia or general population. Subgroup analysis indicated that gender and geographic region may be sources of the assessed studies' heterogeneity. Conclusion: The incidence of schizophrenia is positively correlated with BC, and the incidence of BC in patients with schizophrenia is increased to a certain degree. Because of the effects of potential and publication bias, this conclusion needs more high-quality studies to increase the strength of evidence. (C) 2018 Elsevier Inc. All rights reserved.

e12059 Background: Axillary lymph node (LN) involvement is significantly related with high recurrent risk and influenced by tumor size, histologic grade and subtype in early breast cancer. For hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer without LN involvement, 21-gene recurrence score (RS) provides an effective method evaluating the risk of recurrence and metastasis. But the correlation between RS and LN involvement is not clear currently. To investigate the effect of RS on LN involvement, we designed a retrospective cohort study based on the data of tumor size-match LN+/- HR+HER2- breast cancer. Methods: The luminal type (ER+, PR+ and HER2-) early breast cancer (cT1-2) patients with 1~3 LN+ were enrolled and were tumor size-match paired (1:3) with those LN- during the same period. We compared the 21-gene RS between the LN+ and LN- group by univariate and multivariate analyses. Results: From April 2016 to May 2018, there were 65 LN+ cases undergoing 21-gene test included and 195 LN- cases were paired. With tumor size matched, the LN+ group had significantly younger age, more positive family history, higher histologic grade and higher RS than LN- group. All those factors, excepted histologic grade, were further confirmed in multivariate analysis (Table). Conclusions: After adjusted by tumor size, RS may have a significantly independent correlation with LN involvement in HR+HER2- early breast cancer. Total HR+HER2- cases’ tumor size-match paired (1:3) clinic pathologic and RS data. Clinical trial information: NCT03638648. [Table: see text]

Some progresses have been made in research of long non-coding RNA (hereunder referred to as LncRNA) related to breast cancer. Lots of data about LncRNA transcription concerning breast cancer have been obtained from large-scale omics research (e.g. transcriptomes and chips). Some LncRNAs would become indices for detecting breast cancer and judging its development and prognosis. LncRNAs may affect genesis and development of breast cancer in multiple ways. Perhaps they could develop into potential targets for treating breast cancer if they are carcinogenic. Like those from other studies of breast cancer, many data gained from omics research remain to be validated by much experimental work. For instance, it is still necessary to demonstrate reliability of LncRNAs as indices for diagnosing breast cancer and judging its prognosis (particularly for various subtypes of breast cancer), effectiveness and feasibility of these genes for treating breast cancer as targets. In this paper, recent years' literatures about LncRNAs which are related to breast cancer are summarized and sorted out to review the research progresses in relationships between LncRNAs and breast cancer.

Some progresses have been made in research of long non-coding RNA (hereunder referred to as LncRNA) related to breast cancer. Lots of data about LncRNA transcription concerning breast cancer have been obtained from large-scale omics research (e.g. transcriptomes and chips). Some LncRNAs would become indices for detecting breast cancer and judging its development and prognosis. LncRNAs may affect genesis and development of breast cancer in multiple ways. Perhaps they could develop into potential targets for treating breast cancer if they are carcinogenic. Like those from other studies of breast cancer, many data gained from omics research remain to be validated by much experimental work. For instance, it is still necessary to demonstrate reliability of LncRNAs as indices for diagnosing breast cancer and judging its prognosis (particularly for various subtypes of breast cancer), effectiveness and feasibility of these genes for treating breast cancer as targets. In this paper, recent years’ literatures about LncRNAs which are related to breast cancer are summarized and sorted out to review the research progresses in relationships between LncRNAs and breast cancer.

Background: Metastases to the thyroid gland are uncommon and often occur in patients with advanced metastatic diseases. The management and prognosis of secondary thyroid malignancies (STMs) are not well established. This retrospective study reported the incidence, clinical characteristics, treatment, and prognosis of STM in patients with metastatic tumors. Subjects and Methods: A total of 21 cases (1.2% incidence) diagnosed by fine-needle aspiration between January 2006 to December 2014 in a single center were reviewed. Survival analysis was made by KaplanuMeier method. Results: The primary malignancies included esophagus cancer (7/21, 33.33%), breast cancer (6/21, 28.57%), head and neck cancer (3/21, 14.29%), unknown primary cancer (3/21, 14.29%), and lung cancer (2/21, 9.52%). The mean overall survival (OS) from diagnosis of primary malignancies was 57.26 months (95% confidence interval [CI]: 31.19u83.34) and the 2-year OS rate was 61.9%, and the mean OS from diagnosis of thyroid metastases was 31.20 months (95% CI: 12.23u50.18) and the 2-year OS rate was 34.3%. Patients with the head and neck cancer and breast cancer had better survival than other patients (from diagnosis of primary malignancies, P < 0.001; from diagnosis of thyroid metastases, P = 0.03). Histological types were also related to OS (from diagnosis of primary malignancies, P = 0.039; from diagnosis of thyroid metastases, P = 0.130). In addition, thyroidectomy may improve OS for patients with isolated metastases. Conclusion: The prognosis of STMs basically depends on the anatomic sites and histological types of primary cancers, and thyroidectomy may be considered for patients with isolated metastases.

The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology. The post-operative and biopsy specimens were analyzed for 416 genes using next-generation sequencing, and phosphatidylinositol-3-kinase catalytic α mutation and retinoblastoma loss were evident. Five cycles of etoposide combined with cisplatin were administered and a partial response was achieved. The disease progressed again accompanied with an elevated NSE level, and bronchoscopy examination revealed small cell lung cancer (SCLC) after 3 months. The patient received chemotherapy consisting of irinotecan combined with carboplatin for two cycles and achieved stable disease. Overall, a secondary biopsy is important for the evaluation of genetic and histological changes and the selection of an appropriate treatment following tyrosine kinase inhibitor (TKI) resistance, and NSE may be useful for the early detection of SCLC transformation in cases that are resistant to EGFR-TKI therapy.

Background: As a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported. Objectives: In this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC). Methods: The expression of MALAT1 in clinical samples with TNBC and Her-2 positive breast cancers was tested by qRT-PCR. The statistical analysis was performed to unveil the potential relationships between the expression of MALAT1 and prognostic factors of breast cancer such as OS (overall survival), RFS (relapse-free survival), number of metastatic lymph nodes and pTNM staging in patients with TNBC or Her2 positive breast cancer. MALAT1 and XBP1 were knockdown respectively in Her-2 positive cell line MDA-MB-231, and MALAT1 and Her-2 were knockdown respectively in TNBC cell line MDA-MD-435 using siRNA. The alterations of expressions of MALAT1 and related genes were detected by qRT-PCR in two breast cancer cell lines. The changes of proliferation abilities in two cell lines were observed using CCK8 assays. Furthermore, transwell assays were performed to detect changes to invasion abilities of the cells. Results: The expression of MALAT1 in triple negative and Her-2 positive breast cancers was positively correlated to the number of metastatic lymph nodes in patients with breast cancer. MALAT1 promotes proliferation and invasion abilities of breast cancer cells through XBP1 (X-box binding protein 1)-HIF (hypoxia-inducible factor)-1 alpha pathway in MDA-MB-231 and through Her-2 pathway in MDA-MD-435. Moreover, MALAT1 could possibly be involved in regulation of MYC gene and CD47 (an immune checkpoint gene) in both cell lines. Conclusions: Our study suggested that MALAT1 is a core signaling molecule for promoting development and migration of triple negative and Her-2 positive breast cancers. It would be employed as common markers for prognosis of the two types of breast cancer mentioned above and potential targets for treating them.

Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future.

The aim of the present study was to establish the underlying regulatory mechanism of estrogen receptor (ER) in breast cancer cell gene expression. A gene expression profile (accession no. GSE11324) was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from an estrogen treatment group and a control group were identified. Chromatin immunoprecipitation with high‑throughput sequencing data (series GSE25710) was obtained from the GEO for the ER binding sites, and binding and expression target analysis was performed. A total of 3,122 DEGs were obtained and ER was demonstrated to exhibit inhibition and activation roles during the regulation of its target gene expression. Motif analysis revealed that the upregulated target genes that demonstrated interactions with ER were meis homeobox 1 (MEIS1) and forkhead box P3 (FOXP3). The downregulated target genes, which demonstrated interactions with ER, were thyroid hormone receptor, β (THRB) and grainyhead‑like 1 (GRHL1). Thus, it was observed that ER stimulated gene expression by interacting with MEIS1 and FOXP3, and ER inhibited gene expression by interacting with THRB and GRHL1. However, additional experiments are required to provide further confirmation of these findings.

Background Mucinous breast carcinoma (MC) is a special type of breast cancer that presents with a large amount of extracellular mucin. MC comprises approximately 4% of all invasive breast cancers. This type of tumor has a better prognosis and higher incidence in peri- and post-menopausal patients. Pathologically, there are two main subtypes of MC: pure and mixed. In this study, we describe 10 years of experience with MC at the Zhejiang Cancer Hospital in China, specifically, clinical data, histological findings and immunohistochemical features. Methods We identified MC patients who were diagnosed as operable and completed clinical treatment from January 2001 to January 2011. The clinicopathological data included the age at diagnosis, tumor size, TNM stage, presence and number of lymph node (LN) metastases, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status and p53 expression. If the tumor was defined as mixed mucinous carcinoma (MMC), IHC was performed on a non-mucinous part, such as invasive ductal and lobular cancer. We evaluated the clinical characteristics of all MC patients using chi-square, one-way ANOVA and LSD tests. We also studied the correlations between all of the clinical parameters and LN metastasis in a binary logistic regression analysis. We used ten consecutive years of data that were collected at Zhejiang Cancer Hospital. Results We identified 48 cases of pure mucinous carcinoma (PMC) and 77 cases of MMC. The 48 PMC cases consisted of 38 PMC-A and 10 PMC-B subtypes. The MMCs were divided into two groups, those with partial mixed mucinous breast carcinoma (pMMC, 58 cases) and those with main mixed mucinous breast carcinoma (mMMC, 19 cases). pMMC was defined by tumors with less than 50% mucinous components, while mMMC was defined by tumors where the mucinous component accounted for 50% to 90% of the tumor. No significant differences in the clinicopathological characteristics were noted between the patients with PMC-A and those with PMC-B. The tumor size was larger in the mMMC than PMC cases (44.84 mm vs. 30.06 mm, p = 0.021). The number of positive LN metastases was greater in pMMC than PMC patients (p = 0.024). The clinical stages were significantly different among the three groups, with the pMMC group having more stage III-IV patients than the other two groups (p = 0.005). The incidence of LN metastasis was also higher in the pMMC cases (pMMC vs. mMMC and PMC, 50% vs. 31.58% and 18.75%, p = 0.003). The PMC patients had much lower p53 expression than the other two groups (PMC vs. pMMC and mMMC, 27.08% vs. 55.17% and 57.89%, p = 0.007). The tumor size (>30mm), p53 expression and less proportion of the mucinous component are associated with risk of LN metastasis. Conclusion Based on the results of this study, we conclude that the tumor size, status of LN metastasis, clinical stage, and p53 mutation rate may differ between MMC and PMC patients. The tumor size (>30mm), p53 mutation and less proportion of the mucinous component should be considered risk factors of LN metastasis in MC patients.

Malignant tumors in the tonsils are usually primary. Metastases to the tonsils are extremely rare, with nearly one hundred cases reported. Herein we present an unusual case of palatine tonsillar metastasis of non-small cell lung cancer during chemotherapy. The patient was a 39-year-old man who was diagnosed as non-small lung cancer with IIIA4 staging and poor differentiated histology. After two cycles of vinorelbine and cisplatin based chemotherapy, a big mass was developed in the right palatine tonsil which was pathologically confirmed as the metastasis from the lung. There was no hemorrhage and complains except moderate foreign body sensations. No cervical lymphadenopathy and distal metastases to other organs such as brain and liver was found. Because of poor overall performance status, no radiotherapy was given. The disease progressed after docetaxel treatment. To the best of our knowledge, this is the first case with palatine tonsillar metastasis from non-small lung cancer during induction chemotherapy.

Extramedullary plasmacytoma (EPM) is a plasma cell tumor arising outside of the bone marrow. Solitary EMP is an uncommon neoplasm and rarely occurs in the retroperitoneum and lacks distinctive clinical manifestations. We report a 26-year-old man with a solitary EMP in the retroperitoneum and discuss its clinical features, diagnosis and treatment.