Lung Squamous Adenocarcinoma Research Articles

ADENOSQUAMOUS LUNG CARCINOMA COMPLICATED WITH MARANTIC ENDOCARDITIS AND CHRONIC DISSEMINATED INTRAVASCULAR COAGULATION

Background: Adenosquamous lung carcinoma is a relatively rare subtype of non-small-cell lung cancer that contains both adenocarcinoma (ADC) and squamous cell carcinoma (SCC) components. It is difficult to reach a proper diagnosis before surgery, with the histopathological examination of the resected specimen being the method of choice. A supplementary immunohistochemistry examination of the sample is needed. In order to initiate targeted treatment, molecular testing is mandatory. Case presentation: A 47-year-old female, smoker (15 packs-year), without pathological personal history, presented for fatigue and moderate bilateral leg edema for about 3 months. The blood tests showed severe microcytic, hypochromic anemia and chronic disseminated intravascular coagulation. Computed tomography (CT) scan revealed a tumor in the right basal pleura with secondary pleural effusion, multiple lymphadenopathies, disseminated in the mediastinum, abdominal and pelvic cavity. Two other tumors were noticed, one in the right breast (7 mm) and the other in the vesicouterine pouch (7/10 mm). Prior to lung biopsy, a transthoracic and then transesophageal echocardiography were performed, highlighting the presence of a band on the aortic valve, suggesting marantic endocarditis. Tumor markers were also elevated. In evolution, the patient became bradypsychic, with head CT showing a brain metastasis in the left high-parietal region. Immunohistochemistry examination of the biopsy sample suggested a adenosquamous lung carcinoma. Conclusion: We reported the diagnostic path of a rare subtype of lung cancer in a young female without known comorbidities, with an atypical presentation - multiple extrapulmonary non-metastatic manifestations: metabolic etiology - weight loss, fatigue; vascular and hematological etiology – marantic endocarditis (a very rare complication), severe microcytic, hypochromic anemia and chronic disseminated intravascular coagulation; neurological etiology – peripheral sensorimotor neuropathy of the right arm. A tissue biopsy was performed from the most accessible region – 1/3 inferior right thorax, posterior axillary line. The particularity of the adenosquamous lung carcinoma in this case lies in multiple metastases in less common sites (breast, vesicouterine pouch and probably kidney).

Retracted: Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Retracted: Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Heterogeneity of tumor immune microenvironment and real-world analysis of immunotherapy efficacy in lung adenosquamous carcinoma.

Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration were present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCCs had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort III, the efficacy of ICI-based therapy was estimated using a real-world data of 46 ASCs from 11 centers. Majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. The overall objective response rate of 28%, median progression-free survival of 6.0 months (95% confidence interval [CI] 4.3–7.7), and median overall survival of 24.7 months (95% CI 7.2–42.2) were observed in the ICI-based treatment. This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACCs and SCCCs. Lung ASC patients have a moderate response to ICI-based immunotherapy.

Surgical Options for Resectable Lung Adenosquamous Carcinoma: A Propensity Score-Matched Analysis

BackgroundSurgery is the primary treatment option for Lung adenosquamous carcinoma (ASC) patients. However, no study compares the benefits of lobectomy and sublobar resection in ASC patients.MethodsA total of 1379 patients in the Surveillance, epidemiology, and End Results (SEER) database and 466 patients in Shanghai Pulmonary Hospital (SPH) were enrolled. Survival benefits were evaluated after possible confounders were eliminated by propensity score matching (PSM).ResultsAfter 1:3 PSM, 463 SEER database patients and 244 SPH patients were enrolled. Lobectomy was associated with better overall survival (OS) and disease-free survival (DFS) than sublobar resection for ASC patients (5-year OS of SEER: 46.9% vs. 33.3%, P =0.017; 5-year OS of SPH: 35.0% vs. 16.4%, P =0.002; 5-year DFS of SPH: 29.5% vs. 14.8%, P =0.002). Similar results were observed in stage I patients. Univariate and multivariate Cox regression analyses showed that sublobar resection was an adverse prognostic factor independently (SEER: HR: 1.40, 95%CI: 1.08-1.81, P =0.012; SPH: HR: 1.73, 95%CI: 1.11-2.70, P =0.015). Subgroup analysis showed that all of the ASC patient subtypes tended to benefit more from lobectomy than sublobar resection.ConclusionsLobectomy remains the primary option for ASC patients compared to sublobar resection, including stage I.

Clinicopathological characteristics and prognosis of resectable lung adenosquamous carcinoma: a population-based study of the SEER database.

Adenosquamous carcinoma is a rare subtype of non-small cell lung cancer characterized by aggressive behavior, with combination of adenocarcinoma and squamous cell carcinoma components. The clinicopathological characteristics and prognosis of resectable adenosquamous carcinoma are incompletely understood and this study aimed to depict those in a large population. A total of 805 adenosquamous carcinoma, 7875 squamous cell carcinoma and 23 957 adenocarcinoma patients who underwent lobectomy or sublobectomy were queried from the Surveillance, Epidemiology, and End Results database (2010-17). Clinicopathological characteristics of adenosquamous carcinoma patients were compared with those of squamous cell carcinoma and adenocarcinoma patients. Prognostic factors were identified by univariable and multivariable Cox regression analyses. Propensity score matching was applied to reduce confounding effects. Adenosquamous carcinoma was associated with higher pleural invasion incidence and poorer differentiation compared with squamous cell carcinoma or adenocarcinoma (P values < 0.001). The independent risk factors of cancer-specific survival of adenosquamous carcinoma patients were increasing age, male sex, invading through visceral pleura, poor differentiation and higher stage. Stage IB adenosquamous carcinoma patients whose tumor invaded through visceral pleura had significantly worse survival than those not (P=0.003). Adenosquamous carcinoma patients had worse survival compared with squamous cell carcinoma (5-year-survival: 64.55 vs. 69.09%, P=0.003) and adenocarcinoma (5-year-survival: 64.55 vs. 76.79%, P<0.001) patients before match. And this difference persisted after match. Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients. Visceral pleural invasion status and differentiation grade were vital prognostic factors of adenosquamous carcinoma patients on the basis of stage.

Abstract 5742: The landscape of genetic alteration in Chinese lung adenosquamous carcinoma patients

Abstract Background: Lung adenosquamous carcinoma (LASC) is a mixed histologic component tumor type that contains both squamous cell carcinoma and adenocarcinoma, with each component accounting for at least 10% of tumors. The incidence of LASC is very low, only comprising 0.4-4% of all lung cancers. LASC yields a more aggressive clinical course, and its prognosis is generally worse than that of adenocarcinoma and squamous cell carcinoma of the lung. Due to the rarity of LASC, currently, there is no standard treatment. Also, to date, limited genomic data have been performed. In this study, we analyzed the genomic alterations and clinical signatures of LASC. Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for a targeted, next-generation sequencing (NGS) assay at OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations including single base substitution, indel, copy number variations, and gene fusion and rearrangement were assessed. Results: A total of 124 LASC patients were enrolled in our study, including 77 (62.1%) males and 47 (37.9%) females, with a median age of 61 years old (range 27-82). Forty-three (43, 34.68%) patients had a smoking history and half of patients possessed a Stage III/IV disease. The most commonly altered genes were TP53 (66.9%), EGFR (54.8%), CDKN2A (21%), TERT (21%), and LRP1B (18.5%). Surprisingly, 91.1% and 52.4% patients harbored at least one druggable alteration based on the solid cancer and NSCLC NCCN guides, respectively. The most frequent druggable mutation, EGFR, is comprised of 35 (51.47%) single mutations and 33 (48.53%) complexed mutations, with most containing a 19 exon deletion and EGFR amplification (12%). The median tumor mutational burden (TMB) of patients with LASC was 5.15 muts/Mb (range, 0-69.3 muts/Mb), and 33 (26.6%) patients were TMB-H (TMB ≥ 10 Muts/Mb). Patients with an ARID2, BRCA1, or KEAP1 mutation had a significantly higher value of TMB than wild type (median TMB 16.1 vs. 5 muts/Mb, 29.7 vs. 5 muts/Mb, 14.6 vs. 4.85 muts/Mb, respectively, P &amp;lt; 0.05). Patients with HRR or DDR mutations also displayed a higher TMB value than for wild type. We additionally determined that mutation signature 1 (the clock-like signature), signature 2 (the APOBEC signature), and signature 3 (the BRCA mutational signature) exhibited a higher mutational load for the entire cohort. All patients with signature 2 or 3 displayed a HLA-B heterozygous subtype. Conclusions: Our study revealed genomic profiling for the largest sample size of Chinese LASC patients to date. Profiling obtained from this study demonstrates that LASC patients have the same chance for targeted therapy and immune checkpoint inhibitors as compared to lung adenocarcinoma and lung squamous cell carcinoma, respectively. Citation Format: Hongbiao Wang, Yingcheng Lin, Jun Liu, Yuyin Cai, Xiaofang Qi, Lujia Huang. The landscape of genetic alteration in Chinese lung adenosquamous carcinoma patients [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 5742.

The Effect of Examined Lymph Nodes and Lymph Node Ratio on Pathological Nodal Classification in the Lung Adenosquamous Carcinoma After Lobectomy.

ObjectiveThe effects of examined lymph nodes (LNs) and lymph node ratio (LNR) on pN classification and the prognosis are unclear in lung adenosquamous carcinoma (ASC) patients. Thus, this study aimed to investigate the significance of LNs and LNR in the prognosis of ASC and the impact of the abovementioned factors on the pN classification.MethodsPatients diagnosed with pathological stage T1-4N0-2M0 ASC from the Surveillance Epidemiology and End Results database were included in the study. The primary clinical endpoint was cancer-specific survival (CSS). The optimal cutoff values of the LNs and LNR were determined. An LN indicator, including pN0 #LNs ≤9, pN0 #LNs >9, pN+ #LNR ≤0.53, and pN+ #LNR > 0.53, was developed. Concordance index (C-index) was used to compare the prognostic predictive ability between N classification and LN indicator. The univariable and multivariable Cox regression analyses were used in this study.ResultsThe cohort of 1,416 patients were included in the study. The level of LNs stratified the patients without metastasis of lymph nodes (pN0 #LNs ≤9 vs. pN0 #LNs >9, unadjusted hazard ratio [HR] = 1.255, P = 0.037). Two groups based on the cutoff value of LNR differentiated prognosis of patients with metastasis of lymph nodes (pN+ #LNR >0.53 vs. pN+ #LNR ≤0.53, unadjusted HR = 1.703, P = 0.001). The LN indicator had a much better predictive ability over N classification in this cohort (LN indicator: C-index = 0.615; N classification: C-index = 0.602, P = 0.001).ConclusionsWe explored clinicopathological factors affecting prognosis in resected lung ASC patients. Besides, the LN indicator was confirmed to be played an essential role in affecting the survival rate in ASC patients. The high-level LNs or low-level LNR might be corelated to improved survival outcomes.

Epidemiology and survival outcomes in adenosquamous carcinoma: a population-based study.

The relationship between the location of the primary tumor and survival of adenosquamous carcinoma (ASC) remains poorly understood. This study aimed to evaluate the impact of primary tumor location on the survival outcome of patients with ASC. Patients with ASC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with ≥ 150 cases per tumor location. The Kaplan-Meier method was used to generate survival curves and differences among them were compared using the log-rank test. On the other hand, Cox proportional hazards models were used to evaluate factors that had independent predictive effects on cancer-specific survival (CSS). A total of 14,829 eligible patients with ASC were included in this study. Lung and bronchus ASC accounted for 51.1%, followed by the cervix uteri (17.0%), corpus uteri (13.9%), pancreas (4.9%), esophagus (3.1%), gallbladder (2.5%), stomach (2.2%), colon and rectum (2.0%), head and neck (1.8%), and breast ASC (1.3%). The 5-year CSS of breast, cervix uteri, colon and rectum, corpus uteri, esophagus, gallbladder, head and neck, lung and bronchus, pancreas, and stomach ASC was 76.9%, 66.0%, 34.8%, 72.9%, 12.0%, 10.8%, 45.0%, 24.7%, 4.3%, and 17.3%, respectively. COX analysis demonstrated that the primary tumor location was an independent prognostic factor for CSS. Besides, the breast, uterine corpus, and cervix as well as head and neck ASC were significantly associated with better prognosis, while pancreas and gallbladder ASC were significantly associated with poor CSS; stomach and colorectal were roughly the same as ASC prognosis. Our study showed that the CSS of patients with ASC depends on the location of the primary tumor. Besides, tumor location is an important factor that should guide the use of chemotherapy and radiation.

Heterogeneity of tumor immune microenvironment and real-world analysis of immunotherapy efficacy in lung adenosquamous carcinoma.

e20546 Background: Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. Methods: In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. In cohort II, the efficacy of ICI-based therapy were estimated using a real-world data of 46 ASCs from 11 centers. Results: In cohort I, 22 (73.3%) patients were EGFR-positive. The TIME were defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, PD-L1 and PD-1 were predominantly expressed in SCCC versus ACC, where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration was present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCC had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort II, majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. Overall objective response rate of 28%, median progression-free survival of 6.0 months (95% CI 4.3-7.7), and median overall survival of 24.7 months (95% CI 7.2-42.2) were observed in the ICI-based treatment. Conclusions: This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACC and SCCC. Lung ASC patients have a moderate response to ICI-based immunotherapy.

Risk Factors and Challenging Management of Lung Adenocarcinoma in Young Adult Women: Case Series

Introduction: Lung cancer found in young age is relatively rare with a percentage of cases only 1.4% of overall lung cancer cases in the world. Case: We reported two cases of lung adenocarcinoma in young women aged less than 30. The first case was lung adenosquamous carcinoma in a 28-year-old woman, a passive smoker, who had a family history of cancer. She had the mutation of epidermal growth factor receptor (EGFR) exon 19 deletion and received 1st generation of tyrosine kinase inhibitor. Since the patient was diagnosed at advanced stage with poor performance status, she died within 2 months after being diagnosed. The second case was lung adenocarcinoma in a 23-year-old woman. The patient was a passive smoker and had a history of cancer in the family. She was diagnosed at an advanced stage but with good performance status. The patient underwent chemotherapy with Pemetrexed-Platinum in 6 cycles and 15 cycles of radiotherapy. Conclusion: Lung cancer at a young age is more common in non-smoking female with the histopathology type adenocarcinoma. Non-specific early symptoms become a problem in the early enforcement of lung cancer at a young age. Many cancer-related issues occur in young cancer patient such as premature death, increased dependence on parents, difficulty in school and work due to medication, and reproductive disturbance.

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.

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma.

Background Lung adenosquamous carcinoma (LASC) is a special type of lung cancer. LASC is a malignant tumor with strong aggressiveness and a poor prognosis. Previous studies have revealed that microRNAs (miRNAs) are widely involved in the development of tumors by targeting mRNA. This study is aimed at identifying the key mRNAs and miRNAs of LASC and constructing miRNA-mRNA networks for deeply comprehending the latent molecular mechanisms. Methods mRNA dataset (GSE51852) and miRNA dataset (GSE51853) were extracted and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were picked out by the GEO2R web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted in the DAVID database. The protein-protein interaction (PPI) network was performed and analyzed by using the STRING database and Cytoscape software, respectively. TransmiR v2.0 was applied to predict potential transcription factors of miRNAs. The target genes of DEMs were predicted in the miRWalk database. Results In comparison to normal tissues, a total of 1458 DEGs (511 upregulated and 947 downregulated) and 13 DEMs (5 upregulated and 8 downregulated) were screened out in LASC tissues. The PPI network of the DEGs displayed five key modules and seventeen hub genes. Six target genes of the DEMs were predicted, and five essential miRNA-mRNA regulatory pairs were established. Ensuingly, CENPF, one of the target genes, was also the hub genes of GSE51852, which was obtained from MCODE and cytoHubba and regulated by hsa-miR-205. Conclusions We constructed the miRNA-mRNA regulatory pairs, which are helpful to study the potential regulatory mechanisms and find out promising diagnosis biomarkers and therapeutic targets for LASC.

Adrenal insufficiency resulting from immunotherapy: a rare but life-threatening side effect

A 73-year-old male whom suffers from stage 4 adeno-squamous lung carcinoma with high programmed death-ligand 1 (PD-L1 immunohistochemistry-tumor proportion score (TPS)&gt;50 began his treatment with a type of immune checkpoint inhibitors (ICI) therapy. After 8th cycle of treatment, patient experiences vague symptoms of fever, lethargy and drowsy. Initial working diagnosis was infection and empirical treatment was initiated. Subsequently as patient’s condition did not improve despite appropriate antibiotics, other diagnosis was considered which include adrenal insufficiency and this confirms after checking cortisol level. Hydrocortisone was started promptly and patient clinical condition improved. Decision was to stop ICI treatment interim. Consideration to re-challenge again with ICI may be considered once patient is more fit in the future. Adrenal insufficiency following ICI treatments are rare and misdiagnosed due to its non-specific symptoms. Nonetheless, it comes with high morbidity and mortality. Hence, we wanted to emphasize more on this condition as more elderly patients whom suffers from various type of cancers will be exposed towards ICI treatment.

Needle tract implantation of lung adenosquamous carcinoma after transthoracic fine needle biopsy in a dog

Needle tract implantation of lung adenosquamous carcinoma after transthoracic fine needle biopsy in a dog

Immune heterogeneity in adenocarcinoma and squamous cell carcinoma components of lung adenosquamous carcinoma.

e20523 Background: Lung adenosquamous carcinoma (ASC) is a relatively uncommon malignancy that comprised of both adenocarcinoma component (ACC) and squamous cell carcinoma component (SCCC). We have reported its genomic profile, evolutionary origin, and clinical management. Information of tumor immune microenvironment (TIME) of ASC, including tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), T cell receptors (TCR) repertoire, and PD-L1 status remains scarce. Methods: 28 Surgical ASCs were collected and identified by immunohistochemistry (IHC). ACC and SCCC were obtained separately by microdissection. Targeted sequencing was performed for the two components using a 1021-gene-panel independently. TMB of ACC and SCCC were independently calculated. TMB of ASC calculation was based on aggregation (removing duplicates) of non-synonymous mutations from both ACC and SCCC. TILs and PD-L1were examined by multiplex immunohistochemistry (mIHC). The infiltration level of immune cells in tumor, stroma, and total region (named by both tumor and stroma regions) was investigated. T cell receptor (TCR) repertoires were sequenced and clonality and Shannon index were calculated. Results: SCCC (7.2 mutations/Mb) had a higher TMB level than ACC (6.5 muts/Mb), indicating the immunogenic heterogeneity between the different pathological components. The TMB value of ACC and SCCC were modestly proportional (Spearman r = 0.56, p = 0.001), which was related to the clonal origin. SCCC TMB was lower than the archival LUSC (10.1 muts/Mb), and ACC TMB was similar to LUAD (4.3 muts/Mb). The TMB of ASC was higher than LUAD and close to LUSC. The nonidentical TIL level in ACC and SCCC showed infiltration heterogeneity. For tumor region, CD3+ total T cells, CD4+ T cells, CD8+ T cells, and PD1+ cells accounted for the most proportion of immune cells, with no differences between ACC and SCCC; FOXP3+ CD4+ Treg cells were more abundant in SCCC than ACC ( p = 0.047), as well as CD3+ LAG3+ T cell ( p = 0.029). For stroma region, ACC and SCCC had similar level of CD4+, CD8+, and PD-1 immune cell infiltration; the amount of FOXP3+ CD4 + Treg cells was also higher in SCCC than ACC, as well as CD3+ LAG3+ T cells. For the total region, FOXP3+ CD4 + Treg cells, CD3+ LAG3+ T cells, and PD-1+ T cells were enriched in SCCC compared with ACC, while CD57+ natural killer T (NKT) cells were accumulated with a marginally higher level in ACC ( p = 0.049). TCR repertoires sequencing revealed a lower Shannon’s diversity ( p = 0.029) but higher clonality ( p = 0.047) of SCCC compared with ACC. PD-L1 expression identified by mIHC in SCCC was significantly higher than ACC, in the tumor ( p &lt; 0.001), stroma ( p &lt; 0.001), and total regions ( p &lt; 0.001). Conclusions: SCCC of ASC had higher levels of TMB, Treg cells, TCR clonality, and PD-L1, and similar level of CD3+, CD4+, and CD8+ TILs, comprehensively reflecting the intratumor heterogeneity of TIME.

A case report of right upper lung adenosquamous carcinoma resection following neoadjuvant targeted therapy

The patient was a middle-aged male smoker who had space-occupying lesions in the right upper lung, Positron emission tomography-computed tomography (PET-CT) suggested right upper lung cancer with multiple mediastinal lymph node metastases. Endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) performed in the bronchus of the right apical segment confirmed the lesion as squamous cell carcinoma. Neoadjuvant therapy was planned. Because genetic testing revealed the epidermal growth factor receptor (EGFR) L858R mutation, the possibility of adenosquamous carcinoma was considered. The patient was clinically diagnosed with right upper lung squamous cell carcinoma c-T3N2M0, stage IIIB, and PS 1 point. Dacomitinib was selected for the targeted therapy. Eight weeks after the initiation of treatment, efficacy was assessed as a partial response (PR), suggesting a possibility of R0 resection. After sufficient communication with the patient and his family members, on July 1, 2020, thoracoscopic radical resection of the right upper lung cancer was performed under general anesthesia. Postoperative pathology confirmed adenosquamous carcinoma, of which 80% were adenocarcinoma and 20% were squamous cell carcinoma; no tumor thrombus was seen in the interstitial vessels; and the tumor did not invade the visceral pleura. There was no cancerous infiltration in the bronchial stump of the right upper lung. The following were the results for lymph nodes submitted for examination: L2 (0/1), L4 (0/4), L7 (0/3), L8 (0/7), L10 (0/1), L11 (0/2) and L11 (frozen 0/1) showed no cancer metastasis. The postoperative diagnosis was as follows: adenosquamous carcinoma of the right upper lung p-T2N0M0, stage Ib. After surgery, 4 cycles of the GC (gemcitabine + carboplatin) chemotherapy regimen were given, with continued targeted therapy recommended for 2 years. The patient has been followed-up and is in good condition.

Development and Validation of an LC-MS/MS Method for AC1LPSZG and Pharmacokinetics Application in Rats.

Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC-MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3min per sample. A linear dose-response for quantification was observed over the range of 10-5000ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87-102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6h after collection and stored at -80°C until analysis within 30days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.

The Comprehensive Analyses of Genomic Variations and Assessment of TMB and PD-L1 Expression in Chinese Lung Adenosquamous Carcinoma.

The poor prognosis and fewer treatment option is a current clinical challenge for patients with lung adenosquamous carcinoma (ASC). The previous studies reported that tumor mutational burden (TMB, numbers of mutation per Megabase) is a predictor of clinical response in trials of multiple cancer types, while fewer studies assessed the relationship between TMB level and clinical features and outcomes of lung ASC. Herein, the present study enrolled Chinese patients with lung ASC. DNA was extracted from formalin-fixed paraffin-embedded tumor samples and subjected to next generation sequencing (NGS), and the 457 cancer related genes were evaluated. The results demonstrated that 95 unique genes with somatic variations were identified in the enrolled patients. The top three of high frequency gene mutations were TP53, EGFR, PIK3CA with rates of 62% (13 cases), 48% (10 cases), and 14% (3 cases), respectively. We identified TMB value was significantly correlated with pathological stages (p < 0.05) and invasion of lymph node (p < 0.05). However, TMB value was not significantly correlated to other clinicopathologic indexes, for examples, age, sex, smoking history, tumor size, as well as TP53 and EGFR mutations in lung ASC. Moreover, TMB value was associated with the overall survival (p < 0.01), but not with the relapse-free survival (p = 0.23). In conclusion, this study indicated that lung ASC with high TMB might be associated with the invasion of lymph node and short overall survival. Immunotherapy might be a promising treatment option for lung ASC patients with high TMB.

Research on the Auxiliary Classification and Diagnosis of Lung Cancer Subtypes Based on Histopathological Images

Lung cancer (LC) is one of the most serious cancers threatening human health. Histopathological examination is the gold standard for qualitative and clinical staging of lung tumors. However, the process for doctors to examine thousands of histopathological images is very cumbersome, especially for doctors with less experience. Therefore, objective pathological diagnosis results can effectively help doctors choose the most appropriate treatment mode, thereby improving the survival rate of patients. For the current problem of incomplete experimental subjects in the computer-aided diagnosis of lung cancer subtypes, this study included relatively rare lung adenosquamous carcinoma (ASC) samples for the first time, and proposed a computer-aided diagnosis method based on histopathological images of ASC, lung squamous cell carcinoma (LUSC) and small cell lung carcinoma (SCLC). Firstly, the multidimensional features of 121 LC histopathological images were extracted, and then the relevant features (Relief) algorithm was used for feature selection. The support vector machines (SVMs) classifier was used to classify LC subtypes, and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to make it more intuitive evaluate the generalization ability of the classifier. Finally, through a horizontal comparison with a variety of mainstream classification models, experiments show that the classification effect achieved by the Relief-SVM model is the best. The LUSC-ASC classification accuracy was 73.91%, the LUSC-SCLC classification accuracy was 83.91% and the ASC-SCLC classification accuracy was 73.67%. Our experimental results verify the potential of the auxiliary diagnosis model constructed by machine learning (ML) in the diagnosis of LC.

Growing spheroids of lung adenosquamous carcinoma on electrospun poly(ε-caprolactone)

Lung adenosquamous carcinomas, cell line H125, with an expression of human epidermal growth factor receptor 1 (HER1), were cultured on two scaffolds of poly(ε-caprolactone) produced through electrospinning, one with a nanometric size and the other with a micrometric size. Cytotoxicity, adhesion and proliferation assays demonstrated the non-cytotoxicity of the scaffolds and the capacity of the cells to grow on them. Tumorlike morphology of cells, HER1 expression and the initial formation of invadopodia were detected through fluorescence microscopy. In the nanometric scaffolds, spheroid formation of cancerous cells was observed. Cells cultured in nanometric scaffolds presented higher resistance to cetuximab than those cultured in micrometric ones and also than cells of two-dimensional cultures. This work demonstrated the potentialities of poly(ε-caprolactone) scaffolds for lung adenosquamous carcinoma cultures and is an initial step for further studies on the growth of cancer cell spheroids on electrospun nanofibers.