Yufeng Luo

Pulmonary adenocarcinoma with a micropapillary pattern: a clinicopathological, immunophenotypic and molecular analysis.

Zhang J, Liang Z, Gao J, Luo Y & Liu T u2028(2011) Histopathology 59, 1204–1214 u2028Pulmonary adenocarcinoma with a micropapillary pattern: a clinicopathological, immunophenotypic and molecular analysis

DNAzyme‐mediated cleavage of survivin mRNA and inhibition of the growth of PANC‐1 cells

Background and Aim:u2002 Survivin has functions in both the regulation of cell division and the inhibition of apoptosis, and it is expressed in most human tumors but not in normal adult tissues. It is a potential target for cancer gene therapy. In the present study, we designed a DNAzyme targeting human survivin mRNA and tried to determine its effect on human pancreatic carcinoma cell line PANC‐1.

The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma

Background Lung adenocarcinoma (AD) is a common variant of non-small cell lung cancer (NSCLC). Programmed cell death protein 1/programmed cell death ligand 1 (PD1/PD-L1) are promising immunotherapy targets and its expression may be an important biomarker of predicting clinical response. In this study, we evaluated PD-L1 expression in conjunction with clinicopathological characteristics and outcomes in resected lung adenocarcinoma. Results This study included 133 cases of lung adenocarcinoma. PD-L1 expression rate in lung adenocarcinoma was 16.5% at the mRNA level and 13.5% at the protein level, and the kappa coefficient of the two examination methods was 0.824 (P = 0.219, highly correlated). PD-L1 was highly expressed in male patients and smokers with lung adenocarcinoma (P = 0.019 and 0.002, respectively), while no associations were identified between PD-L1 expression and age, tumor size, clinical stage, positive pleural invasion, lymph node metastasis, or therapy methods. Overexpression of PD-L1 was a significant indicator of shorter recurrence free survival time and overall survival (P = 0.000 and 0.000, respectively). Multivariate analysis revealed that PD-L1 expression was an independent risk factor for poor recurrence free survival and overall survival (P = 0.009 and 0.016, respectively). Materials and Methods Expression of PD-L1 was examined with immunohistochemistry, using the VENTANA PD-L1 (SP263) rabbit monoclonal antibody. mRNA levels of PD-L1 were evaluated using in situ hybridization. Conclusions PD-L1 overexpression is more frequently observed in male patients and smokers in lung adenocarcinoma. PD-L1 expression is an indicator of worse prognosis in surgically resected lung adenocarcinoma patients.

Primary Pulmonary Mucoepidermoid Carcinoma: Histopathological and Moleculargenetic Studies of 26 Cases

Introduction Pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm of the lung and the main salivary gland-type lung carcinoma. The aims of this study were to review the clinicopathological and immunohistochemical features of PMEC and characterize the genetic events in PMEC. Methods We reviewed the pathology cases in our hospital and found 34 initially diagnosed PMEC cases, 26 of which were confirmed as PMEC after excluding 8 cases of MEC-like pulmonary carcinoma. The clinicopathological characteristics of the 26 PMEC cases and the 8 cases of MEC-like pulmonary carcinoma were retrospectively reviewed. MAML2 rearrangement was detected by fluorescence In Situ Hybridization (FISH). Immunostains of ALK, calponin, collagen IV, CK7, EGFR, HER2, Ki-67, Muc5Ac, p63, p40, and TTF-1 were performed. DNA was extracted from 23 cases of PMEC. Mutation profiling of the EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 genes were carried out using next-generation sequencing (NGS), Sanger sequencing, and quantitative polymerase chain reaction (QPCR) in 9 successfully amplified cases. Results Twenty-six cases of PMEC (18 low-grade, 8 high-grade) included 13 men and 13 women aged 12–79 years. Twenty-two cases had a central/endobronchial growth pattern, and 4 cases had a peribronchial growth pattern. Immunohistochemically, CK7, Muc5Ac, p40, and p63 were positive in all cases (26/26);EGFR was positive in 11 cases (11/26); TTF-1, Calponin, HER2 and ALK were negative in all cases (0/26). MAML2 rearrangement was identified in 12 of 18 PMEC cases. No mutations were detected in any of the 7 genes in the 9 cases that qualified for mutation analysis. Twenty-three PMEC patients had follow-up information with a median interval of 32.6 months. Both the 5- and 10-year overall survival rates (OS) were 72.1%, and a high-grade tumor was an adverse prognostic factor in PMEC. There were 8 cases of MEC-like pulmonary carcinoma aged 36–78 years: 2 cases were located in the bronchus, and 6 cases were located in the lung. p63 and TTF-1 were positive in all cases (8/8), p40 was positive in 5 cases (5/8), and ALK was positive in 5 cases (5/8). No cases of MAML2 rearrangement were detected, but there were 5 cases of ALK rearrangement. Conclusions PMEC is a primary malignant pulmonary tumor with a relatively good prognosis that is historically characterized by the presence of mucous cells and a lack of keratinization. There are distinct differences between PMEC and MEC-like pulmonary carcinoma in tumor location preference, immunophenotype, and molecular genetics, and the differential diagnosis is critical due to the therapeutic and prognostic considerations.

Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study

BACKGROUNDnFetal adenocarcinoma of the lung (FLAC) is a rare entity of lung cancer. It is classified into low-grade fetal adenocarcinoma (L-FLAC) and high-grade fetal adenocarcinoma (H-FLAC). We aim to report the clinicopathological and molecular features of FLAC in Chinese patients.nnnMETHODSnFLACs were screened from a consecutive lung adenocarcinoma series comprising 920 cases. The clinicopathological features L-FLAC and H-FLAC were retrospectively reviewed via immunohistochemical study and mutation analysis.nnnRESULTSnThree L-FLAC and five H-FLAC cases were identified. L-FLAC mainly occurred in young patients and was predominantly in stage I upon diagnosis and conferred favorable outcomes. L-FLAC tumors were characterized by the glycogen-rich columnar cells lining the complex glandular structures, with low nuclear atypia, morule formation, and mainly nuclear- and cytoplasmic-localized β-catenin expression. In contrast, H-FLAC predominantly occurred in elderly men with a history of smoking. The stage of H-FLAC was often advanced at presentation and had a poor prognosis. H-FLAC tumors exhibited more prominent atypia of the nucleus, the absence of morule formation, and largely membrane-localized β-catenin. All 5 H-FLACs were immunohistochemically characterized by overexpression of the p53 protein; the L-FLAC tumors were negative for p53. Two cases of H-FLAC were positive for AFP. No Her-2 or ALK-D5F3 overexpression was observed in any of the tumors. EGFR L858R point mutation was identified in one of the H-FLAC cases. EGFR T790M mutation was detected in one of the L-FLAC cases. No mutations in KRAS, PIK3CA or BRAF were detected.nnnCONCLUSIONSnL-FLAC and H-FLAC exhibited distinctive clinicopathological, immunophenotypic and molecular features with potential prognostic value.

Co-existing of adenoid cystic carcinoma and invasive squamous cell carcinoma of the uterine cervix: a report of 3 cases with immunohistochemical study and evaluation of human papillomavirus status.

BackgroundsThe aim of this study was to describe the clinicopathological characteristics and high-risk human papillomavirus (HPV) infection status in patients diagnosed with co-existing of adenoid cystic carcinoma (ACC) and invasive squamous cell carcinoma (SCC) of the uterine cervix.MethodsThree patients were identified from the pathology databank of Peking Union Medical College Hospital from year 2000 to 2014. Immunohistochemistry and in situ hybridization (ISH) were employed in this study.ResultsThe patients were aged 64, 77 and 63xa0years (average, 68xa0years old). All the patients were postmenopausal women who presented with bloody or watery vaginal discharge. The cervical cytology screening results were all suspicious for high-grade squamous intraepithelial lesion (HSIL). The subsequent cervical colposcopy biopsies all showed cervical intraepithelial neoplasia III (CINIII). One patient received only a cervical conization, whereas the other two patients underwent hysterectomy. The immunohistochemical results showed that the ACC compartments were positive for CK7 and CD117; the cases of SCC were negative for CK7 and CD117. P63 staining was strongly positive and diffuse throughout the SCC compartments, whereas only patchy positive areas were observed in the ACC. MYB exhibited strong nuclear staining in the ACC and SCC compartments but negative staining in the endocervical gland. In situ hybridization (ISH) signals for high-risk HPV DNA and mRNA were present in the two compartments of all three patients. The patients had no evidence of disease at an average follow-up time of 21.6xa0months.ConclusionHigh-risk HPV was present in both the ACC and SCC compartments in all three patients.

Clinicopathological analysis of Large Cell Lung Carcinomas definitely diagnosed according to the New World Health Organization Criteria

OBJECTIVEnThe definition of large cell lung carcinoma (LCC) has undergone an extensive modification in the World Health Organization (WHO) Classification (2015). Present study aimed to investigate the clinicopathological characteristics of patients diagnosed as LCC according to current WHO criteria.nnnMETHODSnLCCs diagnosed based on the previous WHO classification were reevaluated, and 17 cases of LCC were finally identified at Peking Union Medical College Hospital and Beijing Chest Hospital between 2009 and 2015. The clinicopathologic features were examined and EGFR and KRAS mutations were tested. Survival of the patients was analyzed by Kaplan-Meier method.nnnRESULTSnThe median age of the patients was 64 years (range: 40-78). Most patients were male (64.7%) and about half of the patients were at TNM stage III (47.1%). Morphologically, most cases (70.6%) were classic LCC. All patients were treated by lobectomy plus lymph node dissection, 2 with bi-lobectomy and 1 with complex lobectomy, and the other 2 patients were further treated by partial pericardiotomy. Ten patients received postoperative chemotherapy, while only 3 patients were treated with radiotherapy after surgery. Molecular analysis showed two cases of EGFR mutation (L858R) but without non-overlapping KRAS mutation. The 3-year overall survival rate was 48.4u202f±u202f15.1%. Chemotherapy was the only predictive factor that is associated with the prognosis of the patients (Pu202f=u202f0.003).nnnCONCLUSIONnThe clinicopathological characteristics of 17 cases of stringently diagnosed LCC were retrospectively analyzed. LCC in our study showed aggressive behavior with high recurrence and metastasis and poor prognosis. Chemotherapy was only predictive factor that is significantly associated with the prognosis of the patients. Future studies based on a larger series and long term follow-up are still needed to characterize it further.

Hormone receptors analysis in Chinese patients with dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare skin tumor. Clinical observations indicated that DFSP has a more aggressive behavior during pregnancy, which suggest there might be a hormonal influence on this tumor. We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) in DFSP patients.

Protein overexpression and gene amplification of cellular mesenchymal-epithelial transition factor is associated with poor prognosis in micropapillary-predominant subtype pulmonary adenocarcinoma

Micropapillary-predominant subtype pulmonary adenocarcinoma (MPPAC) is a subtype of lung cancer with poor prognosis. Cellular mesenchymal-epithelial transition factor (c-MET) is a promising pharmaceutic target found to be associated with the survival of patients with pulmonary adenocarcinoma. In this study, we aimed to analyze c-MET protein overexpression and gene amplification in MPPAC samples and to elucidate their relationship with the clinicopathological characteristics of the patients. c-MET protein expression was examined by immunohistochemical analyses, and gene amplification was detected by fluorescence in situ hybridization. A total of 86 MPPAC cases were included in this study. The prevalence of c-MET protein overexpression and gene amplification were 62.8% and 10.5%, respectively. C-MET protein overexpression was significantly associated with smoking status, lymphatic and venous invasion, and tumor-node-metastasis stage (P = .014, P = .040, and P = .004, respectively), but c-MET gene amplification showed no relation with any of these characteristics. Univariate analysis revealed that pleural invasion, lymph node metastasis, lymphatic and venous invasion, tumor-node-metastasis stage, c-MET protein overexpression, and c-MET gene amplification were associated with poor prognosis (P = .041, P < .001, P = .001, P < .001, P = .001 and P = .001, respectively), but only c-MET gene amplification was an independent prognostic marker (P = .04). These results indicated that c-MET is an important biomarker. Also, c-MET protein overexpression and gene amplification are highly related to poor prognosis in patients with MPPAC.

PD-1/PD-L1 expressions in medullary thyroid carcinoma: Clinicopathologic and prognostic analysis of Chinese population

INTRODUCTIONnFew studies have focused on PD-L1 expression in medullary thyroid carcinoma (MTC). Expressions of PD-1 and PD-L1 and their clinicopathologic and prognostic relevance were therefore further investigated on a relatively large population of MTC patients.nnnMATERIALS AND METHODSnSurgical specimens were obtained from 87 MTC patients during a median follow-up of 37.7 months. PD-1 and PD-L1 expressions on tumor and associated immune cells were studied immunohistochemically using >1% positive cells as a threshold for positivity. Their correlations with clinicopathologic and prognostic feature were analyzed.nnnRESULTSnPD-1 and PD-L1 were positively stained in 22 and 19 MTC patients. Most PD-L1-positive cases (18/19) showed weak to moderate staining intensity. PD-1 and PD-L1 were co-expressed in 11 patients. PD-L1 positivity was significantly correlated with distant metastases at surgery (21.1% vs 1.5%, Pu202f=u202f0.007). Coexpression of PD-1 and PD-L1 in MTC was correlated with advanced pathologic TNM stage III/IV (Pu202f=u202f0.040) and distant metastases at surgery (Pu202f=u202f0.013). However, there was no other clinicopathologic and prognostic relevance regarding to PD-1, PD-L1 or their coexpression in our MTC patients.nnnCONCLUSIONnPD-1/PD-L1 pathway was expressed in MTC patients and was significantly correlated with the distant metastases at surgery, which may shed light on PD-1/PD-L1 as a promising therapeutic target in MTC. Future better understanding of PD-1/PD-L1 expression and their relationship with immunotherapy response may provide direct evidence for management of refractory MTC.