Heparanase Expression Correlates with Angiogenesis and Lymphangiogenesis in Human Lung Cancer

Background and objective Heparanase has been thought to be a good molecular marker of tumor,and the heparanase expression level was correlated closely with tumor metastasis. In this study,we investigate the effects of heparanase on angiogenesis and lymphangiogenesis of lung cancer and the relationship between heparanase expression and vascular endothelial growth factor (VEGF),vascular endothelial growth factor-C (VEGF-C). Methods Immunohistochemistry was used to detect the expression of heparanase,VEGF,VEGF-C protein and microvascular density (MVD),lymphatic vessel density (LVD) in 115 cases of non-small cell lung cancer (NSCLC) and 45 cases of adjacent normal tissue samples. Results Our results showed that heparanase expression was significantly increased in 91 (79.13%) of the 115 cases and correlated with lymph node metastasis (node positive rate 87.0%; node negative rate 36.8%; P=0.003). Heparanase positive expression cases have significantly higher concentration of microvascular density (MVD) and lymphatic vessel density (LVD) as compared with heparanase negative expression cases (P<0.01,P<0.01,respectively),heparanase expression was significantly correlated with VEGF,VEGF-C expression in NSCLC. Conclusion Heparanase overexpression was associated with angiogenesis and lymphangiogenesis of lung cancer,targeting of heparanase may represent a significant therapeutic potential for lung cancer.

Clinical Implications of HER-2 and P53 in Taxane-Based and Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

OBJECTIVE To evaluate the predictive value of humanepidermal growth factor receptor-2 (HER-2) and P53 in taxane-based and anthracycline-based neoadjuvant chemotherapy (NAC)in breast cancer.METHODSSixty-two patients with breast cancer wereincluded in this study.Twenty-two patients were treated withtaxane-based (taxane group) and 40 with anthracycline-based(anthracycline group).ER,PR,c-erbB2 and P53 were detected byimmunohistochemistry staining before NAC,and FluorescenceIn Situ Hybridization(FISH) was used to detect the HER-2 geneamplification for the cases with the expression of c-erbB2 proteinas (++) or (+++).The efficacy of the regimens was evaluated afterNAC.RESULTS In the anthracycline group,objective response (OR)was observed in 30 out of 40 patients (75%),whereas no response(NR) was observed in 10 patients (25%).In the taxane group,ORwas observed in 15 patients out of 22 patients (68.2%),whereasNR was observed in 7 patients (31.8%).HER-2-negative status wascorrelated with a high OR in both taxane-based and anthracycline-based NAC (P = 0.023 and P = 0.029),whereas P53-negative statuswas correlated with high OR rate in anthracycline-based NAC (P= 0.041).The significant difference of the CR rates was observedbetween the patients took<4 cycles and>4 cycles NAC (4.65% vs.21.05%,P<0.05).CONCLUSION The patients with HER-2 gene non-amplicationmay be sensitive to both taxane-based and anthracycline-basedchemotherapy;the patients without P53 overexpression maysuitable to select anthracycline-based chemotherapy;and properincreased NAC cycles may increase CR rates.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.