Sarcomatoid Carcinoma Of Lung Research Articles

Abstract CT262: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: sarcomatoid carcinoma of lung (cohort 11)

Abstract Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be effective in several malignancies but their potential role in rare solid cancers is yet to be established. This study presents the first results of ipilimumab and nivolumab in the sarcomatoid carcinoma of lung cohort (#11) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity are secondary endpoints. Results: Fourteen evaluable patients (median age, 64 years) with sarcomatoid carcinoma lung tumors were analyzed. ORR was 28.6% (4/14) with 1 CR and 3 PRs. The patient with CR has a duration of response (DoR) and OS of 32.4+ months. Three patients with PR showed 100% regression with resolution of one of two non-measurable non-target lesions (DoR 36.8 months), 92% regression (DoR 6.6 months), and 52% regression (DoR 23.0+ months), respectively. Clinical benefit rate (CBR; no progression > 6months) was 50.0% (7/14). The median PFS was 6.1 months, median OS was 10.9 months. The most common adverse events were fatigue and dyspnea (46.2%, n=6 each), and pruritus and hypothyroidism (30.8%, n=4 each). Grade 3-4 adverse events occurred in 30.8% of patients (n=4). There were no adverse events that led to discontinuation. There was one grade 5 adverse event due to respiratory failure. Conclusion: Ipilimumab plus nivolumab in sarcomatoid carcinoma of lung resulted in an ORR of 28.6% and CBR (SD>6 months/PR/CR) of 50.0%, with PFS of 36.9, 32.4+, 23.0+, 17.0, 13.3, 6.6, and 6.6 months. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies are warranted. Citation Format: Young Kwang Chae, Megan Othus, Sandip Patel, Peeran Sandhu, Larry R. Corum, Jeremy P. Cetnar, Shayan Rayani, Anna Moseley, Liam Il-Young Chung, Hye Sung Kim, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: sarcomatoid carcinoma of lung (cohort 11) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT262.

Small bowel obstruction due to lung Sarcomatoid carcinoma: A case study

Small bowel metastases due to lung cancer are extremely rare and predominantly cause intestinal obstruction, perforation and gastrointestinal bleeding. We report the case of a 51-year-old man diagnosed with pulmonary sarcomatoid carcinoma to which an ileal mass was subsequently removed which was found to be compatible with intestinal localization of pulmonary carcinoma.

Small bowel obstruction due to lung Sarcomatoid carcinoma: A case study

Small bowel obstruction due to lung Sarcomatoid carcinoma: A case study

Abstract 207: MET inhibition enhances the effect of radiation in MET mutated non-small cell lung cancer brain metastasis patient derived xenografts

Abstract Objective: The MET receptor is mutated in 3-4% and amplified in 1-6% of patients with non-small cell lung cancer. The most common MET mutation is in exon 14, which results in deletion of the intracellular juxtamembrane domain of the receptor, leading to enhanced signaling. Mutation at Asp-1000 in the juxtamembrane region has also been reported and can lead to inhibition of apoptosis and cell proliferation. MET is involved in multiple pathways associated with radiation response. Therefore, we investigated the effects of inhibiting MET in combination with radiation in two preclinical non-small cell lung cancer (NSCLC) brain metastasis patient derived xenograft (PDX) models. Methods: Surgically obtained tissue was implanted subcutaneously into immunodeficient mice. Histology and DNA loci were compared between original tumor and PDX. DNA sequencing was performed on tumors for mutation analysis. In vivo growth responses to the MET inhibitor capmatinib or savolitinib with and without radiation were assessed. Radiation was delivered in 10 daily fractions of 2 Gy. Drug was administered by oral gavage daily 1 hour prior to radiation at a dose of 2.5 mg/kg for savaolitnib or 20 mg/kg for capmatinib for 10 days. Immunohistochemistry (IHC) was performed to evaluate MET signaling and proliferation. Results: PDXs were successfully established from two patients with MET mutated NSCLC brain metastases: a lung adenocarcinoma with a MET exon 14 skipping mutation and a lung sarcomatoid carcinoma with adenocarcinoma component with an Asp-1000 frameshift mutation. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumors and PDXs. Short tandem repeat analysis confirmed 100% matching of alleles between patient tumors and PDXs. DNA sequencing confirmed METex14 and MET Asp-1000 frameshift mutation. In the METex14 PDX, savolitinib alone significantly inhibited tumor growth with a growth inhibition value of 46% (p<0.01). Combination of savolitinib and radiation significantly delayed growth compared to vehicle control, savolitinib alone or radiation alone (p<0.001). The absolute growth delay was 42.4 days for savolitinib plus radiation treatment compared to 9.3 days for savolitinib alone and 28.2 days for irradiation. In the MET Asp-1000 PDX, capmatinib and radiation significantly delayed growth compared the other treatment arms (p<0.01). IHC demonstrated inhibition of phospho-MET and pS6 and a decrease in Ki67 with MET inhibition. Conclusion: Inhibition of MET enhanced the effect of radiation in our two preclinical in vivo MET mutated NSCLC brain metastasis models. Additional studies are currently underway evaluating the mechanisms of radiation sensitization and the efficacy of this combination in MET amplified PDX models. Citation Format: Kwangok P. Nickel, Shrey Ramesh, Saahil Javeri, Nitin Somasundaram, Nan Sethakorn, Randall J. Kimple, Andrew M. Baschnagel. MET inhibition enhances the effect of radiation in MET mutated non-small cell lung cancer brain metastasis patient derived xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 207.

Clinical and pathological characteristics of 11 NSCLC patients with c-MET exon 14 skipping.

BackgroundThe aim of the present study was to summarize the clinical and pathological characteristics of 11 non-small cell lung cancer (NSCLC) patients with mesenchymal-epithelial transition factor exon 14 skipping (METex14).MethodsFrom 2018 to 2021, medical records of 763 NSCLC patients were reviewed and 11 patients carrying METex14 were identified from the Affiliated Hospital of Guangdong Medical University. Their clinical data were subsequently examined for pathological and related clinical information including symptom and diagnosis, imaging and follow-up.ResultsThe METex14 cohort includes 9 males and 2 females and the age range was 69–85 years, with a median age of 77 years. Of the patients one is diagnosed with stage IVB lung adenosquamous carcinoma, 7 with lung adenocarcinoma (1 with stage IIIA and 6 with stage IV), and 3 with stage IV lung sarcomatoid carcinoma. 3 reached stable disease until the end of follow-up and 4 died within a year due to multiple metastases. In 4 cases, the patients received selective MET inhibitor treatment all lived longer than 7 months. There were 4 heterozygous point mutations and 1 deletion of the MET gene in this cohort, as follows: c.G3028T (p.D1010Y); c.G3028A (p.D1010N); c.G3005C (p.V1002A); c.3022C>G and MET c.3021_3028+20del (E14).ConclusionsAccording to the data that we collected, the incidence of NSCLC carrying METex14 is low and male outnumber female in our sample pool. Selective target therapy had better prognosis than multitargeted tyrosine kinase inhibitor (TKI) such as crizotinib or standard therapy.

Molecular Biology of Lung Carcinosarcoma: A Review of the Literature

Lung Carcinosarcoma (LCS) is a rare, malignant aggressive biphasic tumor with an unfavorable prognosis, high mortality rate, and is composed of a mixture of epithelial and mesenchymal elements. The epithelial or carcinomatous element is most commonly squamous followed by adenocarcinoma, whereas the mesenchymal or sarcomatous element commonly contains the main component of the tumor and shows poorly differentiated spindle cell characteristics. Moreover, other foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be observed. LCS accounts for less than 0.1% of all lung cancers, has a poor prognosis due to late diagnosis and early metastases. It has been estimated that the median survival time is 9 (3-25) months, a prognosis poorer than other non-small cell lung carcinomas (NSCLC). According to the most recent 2015 World Health Organization (WHO) classification, pleomorphic carcinoma, giant cell carcinoma, lung blastoma, spindle cell carcinoma, and carcinosarcoma consist a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies, known as lung sarcomatoid carcinoma, depending on the observed morphology. Although genetic mutations of some common lung cancer subtypes have been extensively investigated, the molecular characteristics of LCS and the existence of abnormal target genes still remain unknown.

Pulmonary sarcomatoid carcinoma - pathohistological and immunohistochemical analysis, prognosis and complex treatment

The pulmonary sarcomatoid carcinoma (PSC) is extremely rarely lung neoplasm. A woman at the age of 55 with a local advanced pulmonary sarcomatoid carcinoma of the right lung and CT data on bilateral adrenal metastases and three brain metastases were established. Diagnosis is placed after bronchoscopy with biopsy and detailed pathochistological and immunohistochemical analysis. PSC is extremely malignant and with high risk of distant haematogenic metastases. This rare clinical case support the need for strict pathohistological and immunohistochemical analysis, a difficult pathohistological differential diagnosis with other primary malignant lung tumors and the assessment of complex treatment. In order to improve the healing results and survival of patients, timely diagnosis is required at early stage with surgical treatment and subsequent adjuvant chemotherapy and targetеd therapy after genetic analysis of surgery or biopsy tissue material.

GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis.

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.

Programmed death ligand-1 expression levels, clinicopathologic features, and survival in surgically resected sarcomatoid lung carcinoma.

To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (P=0.008). No difference in survival was found between PD-L1-positive and -negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giant-cell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.

Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma.

Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p= 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p= 0.2). Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.

The promising role of mucin 4 in association with D2-40 immunohistochemistry in differentiating pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Background Malignant mesothelioma is considered as a rare, aggressive malignant tumor that arises from mesothelial cells of the pleura. Pulmonary spindle cell carcinoma and pleomorphic carcinomas are considered as subtypes of sarcomatoid carcinoma, with an incidence of 2 and 3% of all lung malignancies. The differential diagnosis between sarcomatoid mesothelioma and lung sarcomatoid carcinoma by immunohistochemical markers has not been reached and requires further study. The aim of this study was to investigate the role of mucin 4 (MUC4) and D2-40 in differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma. Materials and methods The cases were divided into 20 cases of sarcomatoid mesothelioma and 14 cases of lung sarcomatoid carcinoma and were immunostained for MUC4 and D2-40 using streptavidin-biotin methods. Results MUC4 expression was seen in tumor cells of 11 (79%) lung sarcomatoid carcinoma cases. All cases of sarcomatoid mesothelioma showed negative immunostaining for MUC4 (0%). D2-40 immunostaining was positive in 16 (80%) cases of sarcomatoid mesothelioma. D2-40 expression was observed in two (14%) lung sarcomatoid carcinoma cases. The negative expression of MUC4 showed 78.57% sensitivity; however, specificity was 100%. The positive expression of D2-40 showed 80% sensitivity and 85.71% specificity. MUC4-negative expression and D2-40-positive expression were statistically significant. Conclusion We conclude that MUC4 and D2-40 immunohistochemical markers can differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma. The combination of the two markers increases sensitivity and specificity for both.

Prognostic factors for sarcomatoid carcinomas of lung: A single-centre experience.

Background:Although lung sarcomatoid carcinomas (LSCa) arised from the epithelial tissue, they have very distinctive features than other non-small cell lung carcinomas in terms of histopathology and survival. It constitutes 0.1%–0.4% of all lung cancers. The aim of our study is to evaluate the survival analysis of LSCa in a single thoracic surgery clinic and to determine the prognostic factors.Materials and Methods:It was a retrospective cohort study. After the approval of the local ethics committee, a total of 34 patients who were operated in our department between January 2010 and December 2018, whose pathologies were reported as sarcomatoid carcinoma was included in the study. The patients were analyzed by age, gender, presence of necrosis in the histopathological examination, tumor stage, tumor diameter, and tumor location.Results:There were 28 males and 6 females. The median age was 60 years (range: 36–80 years). The median survival was 42 months (32.6–52.2 months), and the 5-year overall survival was 33.6%. Significantly negative prognostic factors were tumor diameter and tumor stage (P = 0.003 and 0.001, respectively). Median disease-free interval (DFI) was 38 months (27.3–49.1 months), and 5-year DFI was 32.6%.Conclusion:LSCa are highly heterogeneous epithelial malignancies, and it has worse survival than other epithelial cancers. Relatively, satisfactory results can be obtained in these tumors with surgical treatment.

Prognostic significance of preoperative peripheral blood neutrophil to lymphocyte ratio (NLR) in lung sarcomatoid carcinoma

Background: The present study aimed to evaluate the prognostic value of the neutrophil to lymphocyte ratio (NLR) in patients with lung sarcomatoid carcinoma (LSC). Methods: We retrospectively analyzed the clinicopathological parameters of 100 cases of LSC in the Sun Yat-sen University Cancer Center. Receiver operator characteristics curve analysis was performed to define the cutoff point for the preoperative peripheral blood NLR. The relationship between NLR and the clinicopathological parameters of patients with LSC was estimated using χ2 analysis. Univariate and multivariate statistical analyses were carried out to evaluate the impact of preoperative blood NLR on postoperative survival of patients with LSC. Results: The analyses revealed that the preoperative peripheral blood NLR was significantly associated with tumor size, pN stage, and clinical stage (P vs . 16.0 months, P Conclusions: The preoperative peripheral blood NLR was associated closely with the development and progression of LSC. Patients with an increased NLR were likely to have poor prognosis. Preoperative peripheral blood NLR might function as an important independent prognostic indicator for patients with LSC.

Prognostic significance of preoperative peripheral blood neutrophil to lymphocyte ratio (NLR) in lung sarcomatoid carcinoma.

BackgroundThe present study aimed to evaluate the prognostic value of the neutrophil to lymphocyte ratio (NLR) in patients with lung sarcomatoid carcinoma (LSC).MethodsWe retrospectively analyzed the clinicopathological parameters of 100 cases of LSC in the Sun Yat-sen University Cancer Center. Receiver operator characteristics curve analysis was performed to define the cutoff point for the preoperative peripheral blood NLR. The relationship between NLR and the clinicopathological parameters of patients with LSC was estimated using χ2 analysis. Univariate and multivariate statistical analyses were carried out to evaluate the impact of preoperative blood NLR on postoperative survival of patients with LSC.ResultsThe analyses revealed that the preoperative peripheral blood NLR was significantly associated with tumor size, pN stage, and clinical stage (P<0.05). No relationship was found between NLR and age, gender, smoking, pT stage, pM stage, relapse, and therapy. Preoperative peripheral blood NLR, clinical stage, pT stage, tumor-node-metastasis stage, and tumor size were associated with prognosis in the Kaplan-Meier survival analysis. Patients with a low NLR value had longer survival time than those with a high NLR [mean overall survival (OS) time: 87.1 vs. 16.0 months, P<0.05]. Cox multivariate analysis confirmed that preoperative peripheral blood NLR was an independent indicator for the prognosis of LSC (hazard ratio =3.906, P<0.05).ConclusionsThe preoperative peripheral blood NLR was associated closely with the development and progression of LSC. Patients with an increased NLR were likely to have poor prognosis. Preoperative peripheral blood NLR might function as an important independent prognostic indicator for patients with LSC.

Sarcomatoid carcinoma of lung- rare but dangerous histology - A case series

Sarcomatoid carcinoma of lung- rare but dangerous histology - A case series

1142PD - Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma: Data from a French multicentric cohort

1142PD - Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma: Data from a French multicentric cohort

CD8+ tumor-infiltrating lymphocytes as a novel prognostic biomarker in lung sarcomatoid carcinoma, a rare subtype of lung cancer.

PurposeThe aim of this study was to investigate the degree of infiltration of CD8+ tumor-infiltrating lymphocytes (TILs) including high and low density in lung sarcomatoid carcinoma (LSC) and their clinicopathological significance.Patients and methodsThe density of CD8+ TILs in paraffin-embedded tissue sections from 100 LSC patients was detected by immunohistochemical staining, and the relationship of CD8+ TILs with clinicopathological features and prognosis was analyzed.ResultsThe chi-squared test showed that the degree of infiltration of CD8+ TILs was significantly correlated with the clinicopathological stage and T stage of LSC (P<0.05). The univariate analysis demonstrated that tumor size, clinicopathological stage, T stage, N stage, M stage, and CD8+ TILs are risk factors that affect prognosis of the patients (P<0.05). The mean overall survival (OS) of LSC patients with a high density of CD8+ TILs was 92.3 months, which was significantly higher than 31.2 months in patients with a low density of CD8+ TILs (P<0.05). Cox regression multivariate analysis confirmed that the density of CD8+ TILs was an independent prognostic factor for OS time of LSC patients (hazard ratio=0.455, P<0.05).ConclusionCD8+ TILs could be used as an effective prognostic index for LSC patients, and a high density of CD8+ TILs in tumor tissue may predict a better outcome.

[Expression of anaplastic lymphoma kinase fusion gene in patients with lung sarcomatoid carcinoma and treatment analysis].

Objective: To investigate the expression status of anaplastic lymphoma kinase (ALK) fusion gene in lung sarcomatoid carcinoma (LSC) and the role of ALK inhibitors for treatment. Methods: Total of 84 cases of LSC confirmed by histopathology were detected for ALK fusion gene from January 2011 to December 2014 in the Cancer Hospital of Chinese Academy of Medical Science&Peking Union Medical College and Shandong Zibo Wanjie Cancer Hospital. All patients were primarily treated by the multi-disciplinary mode in combination with chemotherapy or targeted therapy based on surgery. Postoperative adjuvant chemotherapy was given on platinum based two-drug combination regimen. In ALK fusion gene (+ ) patients with recurrence or metastasis, crizotinib target therapy was prefered. Chi-square test was applied for the comparison of 1, 3, 5-year survival rates between the two groups. Results: Eighty-two cases completed the follow-up. ALK fusion gene was found in 9(10.7%) patients. After application of crizotinib, 1 case was evaluated as complete remission, 6 cases as partial response, 2 cases as stable disease; the 1, 3, 5-year survival rate was 100% (9/9), 100% (9/9) and 88.9% (8/9) for the patients with ALK fusion gene, and it was 65.8% (48/73), 15.1% (11/73) and 6.8% (5/73) respectively for patients without ALK fusion gene. There was significant difference in the survival rate between the two groups (χ(2)=1.56, 1.56, 0.83, all P<0.05). Conclusion: ALK fusion gene maybe expressed in LSC patients. Compared with conventional chemotherapy, crizotinib can significantly prolong the survival time of patients with ALK fusion gene.

The Hidden Genomic and Transcriptomic Plasticity of Giant Marker Chromosomes in Cancer.

Genome amplification in the form of rings or giant rod-shaped marker chromosomes (RGMs) is a common genetic alteration in soft tissue tumors. The mitotic stability of these structures is often rescued by perfectly functioning analphoid neocentromeres, which therefore significantly contribute to cancer progression. Here, we disentangled the genomic architecture of many neocentromeres stabilizing marker chromosomes in well-differentiated liposarcoma and lung sarcomatoid carcinoma samples. In cells carrying heavily rearranged RGMs, these structures were assembled as patchworks of multiple short amplified sequences, disclosing an extremely high level of complexity and definitely ruling out the existence of regions prone to neocentromere seeding. Moreover, by studying two well-differentiated liposarcoma samples derived from the onset and the recurrence of the same tumor, we documented an expansion of the neocentromeric domain that occurred during tumor progression, which reflects a strong selective pressure acting toward the improvement of the neocentromeric functionality in cancer. In lung sarcomatoid carcinoma cells we documented, extensive "centromere sliding" phenomena giving rise to multiple, closely mapping neocentromeric epialleles on separate coexisting markers occur, likely due to the instability of neocentromeres arising in cancer cells. Finally, by investigating the transcriptional activity of neocentromeres, we came across a burst of chimeric transcripts, both by extremely complex genomic rearrangements, and cis/trans-splicing events. Post-transcriptional editing events have been reported to expand and variegate the genetic repertoire of higher eukaryotes, so they might have a determining role in cancer. The increased incidence of fusion transcripts, might act as a driving force for the genomic amplification process, together with the increased transcription of oncogenes.

Overexpression of p53R2 is associated with poor prognosis in lung sarcomatoid carcinoma

BackgroundThis study aimmed to evaluate the expression of p53-inducible RR small subunit 2 homologue (p53R2) in Lung sarcomatoid carcinoma (LSC) and its association with clinicopathological parameters and prognosis.MethodsIn this study, clinicopathological factors and prognostic significance of the expression of p53R2 was investigated by immunohistochemistry (IHC) in 100 cases of LSC.ResultsThe results showed that the expression of p53R2 was significantly correlated with clinical stage (P<0.05). But there was no statistically correlation with gender, age, smoking, tumor size, pT stage, pN stage, pM stage, therapy and relapse. Kaplan-Meier analysis revealed that the expression of p53R2, clinical stage, pT stage, pN stage, pM stage and tumor size were closely related to patients’ survival, and the analysis also revealed that patients with low expression of p53R2 had a longer overall survival than that with high expression (Mean overall survival: 84.8 months vs. 34.7 months, P<0.05). Further multivariate analysis indicated that the expression of p53R2 was identified as an independent prognostic factor in the prediction of the overall survival for patients with LSC (HR = 3.217, P<0.05).ConclusionsThe expression of p53R2 was inversely associated with the proliferation and progression of LSC, and the results indicated that the high expression of p53R2 was an independent factor for unfavorable prognosis of patients with LSC.