Architectural Grade Research Articles

Prognostic value of large amino acid transporter type 1 (LAT1) expression in pulmonary adenocarcinoma: A tissue microarray study

BackgroundLarge amino acid transporter type 1 (LAT1) provides cancer cells with essential amino acids for both protein synthesis and cell growth and may predict patient prognosis. Additionally, LAT1 inhibition can be a therapeutic target. This study aimed to examine the prognostic significance of LAT1 expression in lung cancer, paying special attention to adenocarcinoma subtypes. MethodsTissue microarrays (TMA) of 1,560 total cores obtained from surgically resected lung cancer specimens between 1995 and 2008 at our hospital were used. Overall, 795 cases of adenocarcinoma were identified, and 717 underwent further evaluation. Immunohistochemical staining of whole slides and TMA cores were assessed to set H-score cutoff value.. Immunohistochemical expression of LAT1 was examined based on the subtypes of adenocarcinoma. Statistical analyses explored the prognostic significance of LAT1. ResultsAdenocarcinoma accounted for 71.8% of all cases (n = 795), and 216 cases (27.1%) expressed LAT1. The 795 cases were categorized into five subtypes: lepidic (n = 29, 3.6%), papillary (n = 601, 75.6%), acinar (n = 58, 7.3%), and solid (n = 9, 1.1%); 717 of the 795 cases were further assessed according to the exclusion criteria. The LAT1-positive ratio increased as the architectural grade increased. Notably, in papillary adenocarcinoma, the LAT1-positive group had significantly lower overall survival compared to the negative group (10-year survival: 45.6% vs. 60.8%, p < 0.001). ConclusionLAT1 expression was higher in high-grade subtypes of pulmonary adenocarcinoma. Moreover, LAT1 expression is useful for predicting prognosis, particularly in papillary adenocarcinoma, facilitating prognostic stratification of papillary adenocarcinoma.

Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease.

Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcystic features, 23 (55%) were stage pT3a or higher. Most tumors had strong and diffuse cytoplasmic immunoreactivity for CK7 (93%, 37/40) and AMACR (100%, 40/40). Fumarate hydratase staining was retained in all cases tested (39/39). We performed next-generation sequencing on 15 of these cases with available tissue and identified chromosomal alterations commonly reported in historically "type 1" PRCC, notably multiple chromosomal gains, particularly of chromosomes 7 and 17, and MET alterations. However, alterations in pathways associated with more aggressive behavior (including SETD2, CDKN2A, and members of the NRF pathway) were also identified in 6 of 15 cases tested (40%). Given this molecular and immunophenotypic data, we subsequently reviewed an additional group of 60 consecutive pT2b-pT3 PRCCs to allow for comparisons between cases with and without microcysts, to assess for potential associations with other recently described histologic patterns (ie, "unfavorable architecture": micropapillary, solid, and hobnail), and to assess interobserver reproducibility for diagnosing architectural patterns and grade. Of the total combined 102 PRCCs, 67 (66%) had microcystic architecture within the intrarenal component but were commonly admixed with other patterns (39% had micropapillary, 31% solid, and 31% hobnail). Twenty-seven cases (26%) had metastatic disease, and 24 of these 27 (89%) had microcystic architecture in the intrarenal tumor. Within the pT3 subset, 21 of 22 cases with metastases (95%) had extrarenal invasion as either individual microcysts in renal sinus fat or aggregates of microcysts bulging beyond the confines of the capsule. Backward elimination and stepwise regression methods to detect features significantly associated with adverse outcome identified solid architecture (hazard ratio [HR]: 6.3; confidence interval [CI]: 2.1-18.8; P=0.001), hobnail architecture (HR: 5.3; CI: 1.7-16.7; P=0.004), and microcystic architecture at the tumor-stromal interface (HR: 4.2; CI: 1.1-16.7; P=0.036) as strongest. Of architectural patterns and grade, the microcystic pattern had a substantial interobserver agreement (κ score=0.795) that was highest among the 6 observers. In summary, PRCCs with microcystic architecture represents a subset of historically "type 1" PRCC with a predilection for morphologically distinctive extrarenal involvement and metastatic disease. Microcysts co-vary with other "unfavorable" architectural patterns also associated with higher risk for aggressive disease (ie, micropapillary, hobnail, and solid), but microcysts were more common and have superior interobserver reproducibility. These findings suggest that microcystic PRCC should be recognized as a potentially aggressive histologic pattern of growth in PRCC.

The Underlying Tumor Genomics of Predominant Histologic Subtypes in Lung Adenocarcinoma.

The purpose of the study is to genomically characterize the biology and related therapeutic opportunities of prognostically important predominant histologic subtypes in lung adenocarcinoma (LUAD). We identified 604 patients with stage I to III LUAD who underwent complete resection and targeted next-generation sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform. Tumors were classified according to predominant histologic subtype and grouped by architectural grade (lepidic [LEP], acinar or papillary [ACI/PAP], and micropapillary or solid [MIP/SOL]). Associations among clinicopathologic factors, genomic features, mutational signatures, and recurrence were evaluated within subtypes and, when appropriate, quantified using competing-risks regression, with adjustment for pathologic stage and extent of resection. MIP/SOL tumors had higher tumor mutational burden (p < 0.001), fraction of genome altered (p= 0.001), copy number amplifications (p= 0.021), rate of whole-genome doubling (p= 0.008), and number of oncogenic pathways altered ( p < 0.001) as compared with LEP and ACI/PAP tumors. Across all tumors, mutational signatures attributed to APOBEC activity were associated with the highest risk of postresection recurrence: SBS2 (p= 0.021) and SBS13 (p= 0.005). Three oncogenic pathways (p53, Wnt, Myc) were altered with statistical significance in MIP/SOL tumors. Compared with LEP and ACI/PAP tumors, MIP/SOL tumors had a higher frequency of targetable BRAF-V600E mutations (p= 0.046). Among ACI/PAP tumors, alterations in the cell cycle (p < 0.001) and PI3K (p= 0.002) pathways were associated with recurrence; among MIP/SOL tumors, only PI3K alterations were associated with recurrence (p= 0.049). These results provide the first in-depth assessment of tumor genomic profiling of predominant LUAD histologic subtypes, their associations with recurrence, and their correlation with targetable driver alterations in patients with surgically resected LUAD.

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR(OS):2.09; HR(DFS):1.52) and STAS (HR(OS):1.51; HR(DFS):1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.

Clinicopathological variables influencing overall survival, recurrence and post-recurrence survival in resected stage I non-small-cell lung cancer

BackgroundTo investigate clinicopathological variables influencing overall survival, overall recurrence, and post-recurrence survival (PRS) in patients who experienced curative-intent surgical resection of stage I non-small-cell lung cancer (NSCLC).MethodsWe investigated a series of 1387 patients with stage I NSCLC who underwent surgical resection from 2008 to 2015. The effect clinicopathological factors on death, recurrence, and PRS were evaluated by Kaplan-Meier estimates and cox regression analysis.ResultsAmong the 1387 stage I patients, 301 (21.7%) experienced recurrence. The 5-year cumulative incidence of recurrence (CIR) for all patients was 20.2% and median PRS was 25.5 months. The older age (P = 0.036), p-stage IB (P = 0.001), sublobar resection(P<0.001), histology subtype (P<0.001), and lymphovascular invasion (LVI) (P = 0.042) were significantly associated with worse overall survival. Among 301 recurrent patients, univariable analysis indicated that p-stage IB (versus IA) (P<0.001), LVI (P<0.001) and visceral pleural invasion (VPI) (P<0.001) were remarkably correlated with the higher incidence of recurrence. Taking the effect of clinicopathological variables on PRS into consideration, smoking history (P = 0.043), non-adenocarcinoma (P = 0.013), high architectural grade of LUAD (P = 0.019), EGFR wild status (P = 0.002), bone metastasis (P =0.040) and brain metastasis (P = 0.042) were substantially related with poorer PRS. Multivariate analysis demonstrated that high architectural grade of LUAD (P = 0.008), brain metastasis (P = 0.010) and bone metastasis (P = 0.043) were independently associated with PRS.ConclusionIn patients with resected stage I NSCLC, the older age, p-stage IB (versus IA), sublobar resection, histology subtype, and LVI were significantly associated with worse overall survival. P-stage IB (versus IA), LVI, and VPI were significantly correlated with the higher incidence of recurrence. High architectural grade of LUAD, brain metastasis and bone metastasis were independent risk factors with PRS.

Traces of intact paraben molecules in endometrial carcinoma.

Endometrial carcinoma is the most commonly encountered gynecological cancer in women worldwide and is also one of the popular models of the hormone-dependent carcinomas. This study was aimed to evaluate and compare the concentrations of five paraben molecules (methylparaben, ethylparaben, N-propylparaben, benzylparaben, isobutylparaben + N-butylparaben) in the endometrial and myometrial tissue samples of patients diagnosed with endometrial carcinoma and benign gynecologic diseases. A total of 88 patients were included in the study and chemical analysis was performed on 176 tissue samples. The study group comprised of 33 patients with endometrial carcinoma and 6 patients with endometrial intraepithelial neoplasia. The control group comprised of 49 patients. One endometrial and one myometrial tissue samples were collected from each patient. The analyses were performed using ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). At least one type of paraben molecule was detected in 23.07% (9/39) of the patients in the study group, and in 2.04% (1/49) of the patients in the control group; this difference between the groups was statistically significant (p = .002). N-Propylparaben and isobutyl + N-butylparaben were the most frequently detected (in 7/10 of the samples) paraben molecules in the study. Tumor characteristics (tumor diameter, myometrial invasion, architectural grade, nuclear grade, lymphovascular space invasion, and tumor stage) were comparable between the two groups of endometrial carcinoma (paraben-detected and paraben-undetected groups). In conclusion, paraben molecules were more frequently detected in the endometrial carcinoma tissue samples than in the normal endometrium.

Prognostic significance of solid growth in endometrioid endometrial adenocarcinoma.

Endometrioid endometrial cancer is the most common histological subtype of endometrial adenocarcinoma. In the FIGO grading scheme, both architectural and nuclear grade are taken into consideration. However, the specific impact of solid growth alone on endometrioid endometrial adenocarcinoma outcome is not well documented. We sought to assess the degree of impact of solid growth on lymphovascular space invasion (LVSI), myometrial invasion, tumor size, FIGO stage, lymph node metastasis (LNM), relapse-free survival (RFS) and disease-specific survival (DSS). Paraffin blocks of 269 patients treated for endometrioid endometrial cancer were retrospectively analyzed with morphometry for solid growth percentages. A statistically significant cut-off value of 1% solid growth was found for predicting LNM and advanced stage (III or IV), myometrial invasion and LVSI (p < 0.001) and a cut-off value of 8% was found for predicting adverse survival outcome (p < 0.001). The mean DSS was significantly higher in patients with < 6% solid growth compared to patients with 6-50%, 51-75% and > 75% solid growth (p < 0.001). Although, the mean RFS and DSS were lowest in patients with 51-75% solid growth, this did not reach statistical significance in comparison to 6-50% and > 75% (p > 0.05). Although > 75% solid growth was most significantly associated with many of the adverse prognostic factors, this subset did not provide prognostic superiority in predicting adverse survival when compared to subsets within 6-75% solid growth. In conclusion, although no statistically significant difference in survival was found among subdivisions of architectural grades 2 and 3, solid growth, especially ≥ 8%, appeared to be an independent prognostic factor for survival in patients with early-stage endometrioid endometrial cancer.

Predictive Value of Histologic Characteristics on Hormone Receptor and HER-2 Status of Patients with Invasive Breast Carcinoma, No Special Type, in an Academic Medical Center

Objective: This study aims to assess the predictive value of histologic characteristics in determination of hormone receptor (ER/PR) and HER-2/Neu status in patients with invasive breast carcinoma of no special type (NST). Methodology: A 4-year review of histopathology and immunohistochemistry reports of women diagnosed with invasive carcinoma NST, was done. Multiple logistic regression was used to determine the association between histologic characteristics and ER and PR status, while multinomial multiple logistic regression was used to determine the association between histologic characteristics and HER-2 status, and that between ER and PR expression, and HER-2 immunoreactivity. All analyses included age, pathologic tumor size, lymph node stage, and lymphovascular space invasion as covariates. Results: A total of 137 cases were included in the study. Architectural grade is a significant positive predictor of equivocal HER-2 status ( P =0.026). Nuclear grade is a significant negative predictor of ER status ( P =0.031). Elston score and Nottingham histologic grade showed no significant association with hormone receptor and HER-2 status. ER status demonstrated no significant association with HER-2 expression, but PR status appears to be a significant negative predictor of a strongly positive HER-2 status ( P =0.035). Lymph node stage seems to be a significant positive predictor of an equivocal HER-2 status. Conclusion: Histologic characteristics can predict ER, PR, and HER-2 status, and interactions between expression of these markers provide some insights regarding the complex genetic interactions in the pathogenesis of breast cancer, and its translation into different histologic phenotypes.

A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites.

Access to tissue in patients with hepatocellular carcinoma (HCC) is limited compared to other malignancies, particularly at advanced stages. This has precluded a thorough characterisation of molecular drivers of HCC dissemination, particularly in relation to distant metastases. Biomarker assessment is restricted to early stages, and paired primary-metastatic comparisons between samples from the same patient are difficult. We report the evaluation of 88 patients with HCC who underwent autopsy, including multiregional sampling of primary and metastatic sites totalling 230 nodules analysed. The study included morphological assessment, immunohistochemistry and mutation status of the TERT promoter, the most frequently mutated gene in HCC. We confirm a strong predilection of HCC for lung dissemination, including subclinical micrometastases (unrecognised during imaging and macroscopic examinations) in 30% of patients with disseminated disease. Size of dominant tumour nodule; multinodularity; macrovascular invasion; high histological, nuclear and architectural grades; and cellular crowding were associated with the presence of extrahepatic metastasis. Among the immunohistochemistry markers tested, metastatic nodules had significantly higher K19 and EpCAM expression than primary liver tumours. Morphological and immunohistochemical features showed that metastatic HCC could be traced back to the primary tumour, sometimes to a specific hepatic nodule. This study suggests limited heterogeneity in metastatic sites compared to primary tumour sites.

Endoscopic and clinicopathological features of intramucosal, histologically mixed-type, low-grade, well-differentiated gastric tubular adenocarcinoma with the potential for late-onset lymph node metastasis

BackgroundIntramucosal, histologically mixed-type, low-grade (LG), well-differentiated gastric tubular adenocarcinomas (tub1s; LG-tub1s) have larger mean diameters and exhibit a higher frequency of the gastric mucin phenotype (G-phenotype) than pure LG-tub1s. In proportion to their increases in diameter, G-phenotype differentiated-type early gastric cancer (EGC) tumours reportedly grow to eventually contain (an) undifferentiated-type component(s) and LG-tub1s, which are included in differentiated-type EGCs, reportedly exhibit changes in their glandular architectural and cytological atypia grades from LG to high-grade (HG) and can grow to contain a moderately differentiated tubular adenocarcinoma (tub2) component and undifferentiated components. Because they generally show a higher frequency of malignancy relative to tumours with a higher atypia grade and lower differentiation degree, it is suggested that, among mixed-type LG-tub1s, G-phenotype LG-tub1s containing an HG-tub2 component (LG-tub1s > HG-tub2) with undifferentiated components might lead to late-onset metastasis to lymph nodes even after a successful endoscopic submucosal dissection (ESD). We aimed to clarify the endoscopic and clinicopathological features of these G-phenotype LG-tub1s > HG-tub2.MethodsOf the 13,217 oesophagogastroduodenoscopies performed at our institutions between September 2008 and March 2016, 185 EGC lesions were evaluated in this retrospective observational study. Among these EGC lesions, 60 intramucosal LG-tub1s were divided into 53 tub1 (44 pure LG-tub1s and nine LG-tub1s containing HG-tub1) lesions and seven LG-tub1 > tub2 (LG-tub1 containing LG- and HG-tub2) lesions.ResultsThe frequencies of the superficial depressed type (P = 0.026), reddish colour (P = 0.006), HG of contained tub2s (P = 0.006), and G-phenotype (P = 0.028) were significantly higher in the LG-tub1 > tub2 group than those in the tub1 group. However, the largest lesion of the LG-tub1 > tub2 group had a superficial flat appearance, an isochromatic colour, an HG-tub2 and an undifferentiated component, and a large diameter greater than 30 mm, and it exhibited a G-phenotype.ConclusionsIntramucosal G-phenotype LG-tub1s > HG-tub2 are potential premalignant stomach neoplasms that may have specific endoscopic and clinicopathological features. However, G-phenotype LG-tub1s > HG-tub2 with undifferentiated component, which potentially show higher malignancy than those without undifferentiated components might change from a reddish to isochromatic colour. Accurately diagnosing, treating, and following-up G-phenotype LG-tub1s > HG-tub2 might decrease the number of patients who experience late-onset metastasis after ESD.

P1.09-19 Positive Correlation Between Whole Genomic Copy Number Variant Scoring and the Grading System in Lung Non-Mucinous Invasive Adenocarcinoma

Grading systems of Lung adenocarcinoma have been proposed by Sica and Kadota in stage I tumors,but the predominant architectural subtypes grading system is applicable for resection samples mostly. The correlation between the histological subtypes and grading with whole genomic copy number variation(WGCNV) is unknown, and was investigated in lung non-mucinous invasive adenocarcinoma (LNMIA) at this study. The predominant histological subtype from 58 resection specimens of LNMIA and 20 para-cancerous lung tissues were collected by laser microdissection from HE staining FrameSlides PEN-Membrane slides.7 of 58 specimens,two predominant subtypes in one cancerous nodule were collected simultaneously. Whole genome amplification followed by high-throughput sequencing was used to deteted WGCNV with the para-cancerous lung tissues as normal reference set and WGCNV was scored by a particular formula. WGCNV median scores of 5 histological subtypes of LNMIA with three tiered architectural grades are shown in Table1. The WGCNV scores have a positive correlation with either histological subtypes and architectural grading system (Figure1 A and B). The differences of WGCNV scores are detected betweem two predominant subtypes in one cancerous nodule. GWCNV scores display a positive correlation with three tiered architectural grading system and may has a potential value to predict prognosis in LNMIA.

Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

Objective:To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer.Material and Methods:Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman’s rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis.Results:Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis.Conclusion:Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and IsAssociated with a Poor Prognosis.

Expression of breast cancer metastasis suppressor 1 gene (BRMS1) is decreased in NSCLC cells and tumors. We hypothesized that intratumoral breast cancer metastasis suppressor 1 (BRMS1) expression is associated with lung adenocarcinoma (LUAD) histologic subtypes and overall survival (OS) and disease-free survival (DFS) in patients undergoing resection for early-stage LUAD. Patients (N= 1030) who underwent complete resection for LUAD with tissue available for histologic evaluation were identified. Tissue microarrays were constructed, and immunostaining was performed and scored for intensity of BRMS1 expression. OS and DFS were estimated (by the Kaplan-Meier method) and compared between groups (by the log-rank test), stratified by stage. Hazard ratios (HRs) for hazard of death and recurrence were estimated using univariable and multivariable Cox proportional hazards models. OS and DFS nomograms were created, and model performance was examined. Intratumoral BRMS1 expression was high in 632 patients (61%) and low in 398 (39%). Low BRMS1 expression was associated with higher pathologic T stage (p= 0.001), larger tumor size (p ≤ 0.0001), greater lymphatic (p= 0.032) and vascular (p= 0.001) invasion, LUAD histologic subtype (p= 0.001), and intermediate and high architectural tumor grade (p= 0.003). Low BRMS1 expression was an independent predictor of worse OS (HR= 1.35, 95% confidence interval: 1.10-1.65, p= 0.004) and DFS (HR= 1.27, 95% confidence interval: 1.05-1.54, p= 0.012). OS and DFS nomograms showed excellent predictive performance based on discrimination and calibration. Among patients with surgically resected LUAD, OS and DFS were significantly worse in cases with low intratumoral BRMS1 expression. Our findings suggest that BRMS1 is an independent biomarker with prognostic significance in surgically resected LUAD.

Evaluation of grading systems in stage I lung adenocarcinomas: a retrospective cohort study

AimsThere is no internationally accepted grading system for lung adenocarcinoma despite the new WHO classification. The architectural grade, the Kadota grade and the Sica score were evaluated and compared with...

P2.03b-003 Mutation Profile & Histology According to ERS/ATC/IASCL Associated with IPFS to WBI in BM Patients with Recent Adenocarcinoma Lung Cancer: Topic: Brain Meta

Brain-metastases (BM) are a common metastatic site in non-small-cell lung cancer (NSCLC). We studied the impact of genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR), intracranial-progression-free survival (IPFS) and overall-survival (OS) after whole-brain irradiation (WBI) in patients at recently diagnosis with NSCLC and BM. From 2009-2015, 231 NSCLC patients with BM were reviewed for eligibility. Among them, 121 patients with recently diagnosis of NSCLC, were treated with WBI and have available genotyping status. EGFR, KRAS, ALK and WT patients were found in 38.0%, 6.6%, 5.8% and 49.6%, respectively. Overall, ORR and disease control rate (DCR) were 62.0% and 76.8%, respectively. ORR for EGFR, KRAS, ALK and WT patients were 82.6%, 25.0%, 71.4% and 50.0%, respectively (p=0.001). Female gender (OR 2.22 [95% CI: 1.01 – 4.89] P=0.047) and EGFR were associated to better response to WBI (OR 5.67 [95% CI 2.0-15.8], P = 0.001). A high architectural histological grade was independently associated with resistance to WBI. Median IPFS was 9.06 months [95% CI 6.5 -11.4]. IPFS for EGFR, K-RAS, ALK and WT patients were 11.9, 4.6,12.5 and 6.6 months, respectively (P <0.0001). EGFR mutation status (HR 0.54 [95%CI 0.3-0.9], P = 0.030) was the only factor associated with higher IPFS in the multivariate Cox-regression analysis. Median OS was 16.6 months [95% CI 11.6-22.6]. OS for EGFR, ALK, KRAS and WT patients were 26.8, 13.5, 4.9 and 13.6 months, respectively (P < 0.001). Intracranial OR was associated with a higher OS (HR 0.28 [95%CI 0.2-0.5], P < 0.001), while KRAS mutation positive status (HR 3.45 [95%CI 1.4-8.4], P = 0.006) was independently associated with worse OS. EGFR mutation is an independent predictive factor for OR to WBI for BM in patients with NSCLC. KRAS mutation is an independent predictive factor for worse OS after BM.

Axalta adds new architectural grade to its Alesta AR line

Axalta adds new architectural grade to its Alesta AR line

Aldehyde dehyderogenase (ALDH1A1) delineating the normal and cancer stem cells in spectral lung lesions: An immunohistochemical appraisal

Background and aimALDH1A1 is one of the promising cancer stem cell markers, it has been found in different cancers, including lung cancer. We aimed to assess its immunohistochemical expression in spectral lung lesions (neoplastic versus non neoplastic) and to correlate its expression with certain pathological parameters (e.g. histopathological type and tumor grade). Materials and methodsThe study included 105 specimens of spectral lung lesions (20 adjacent normal tissues, 64 non small cell carcinoma (NSCLCs), 16 small cell carcinoma (SCLCs) and six inflammatory pseudotumors, in addition to nine metastatic tumors to lymph nodes. Both H&E and immunohistochemical stained sections were assessed and evaluated according to quick immunoreactivity score. ResultsALDH1A1 expression showed a broad dynamic range of immunoreactivity score (0–8) in different types of lung cancers with strong reactivity of normal stem cells. Significant statistical associations were found between ALDH1A1 expression and squamous cell carcinoma & SCLC (p=0.02 and 0.003, respectively), with very high mean percentage of positive cells in SCLC (58.50±10.62), followed by adenocarcinoma and squamous cell carcinoma (38.37±35.12 and 22.77±13.89, respectively). Adenocarcinomas were classified according to the IASLC/ATS/ERS classification and grouped by architectural grade into low, intermediate and high. Heterogeneity of ALDH1A1 immunoreactivity scores within adenocarcinoma can reflect histological patterns heterogeneity with a strong association to the grade. Strong diffuse expression was seen in inflammatory pseudotumors and impressive membranous expression was noticed in metastatic tumors. Important pitfalls of ALDH1A1 immunostaining were applied for accurate interpretations. ConclusionWe ascertained the presence of strong association between ALDH1A1 expression and both histological subtype & tumor grade of NSCLCs. We report a fascinating finding; ALDH1A1 heterogeneity within adenocarcinoma can be mapped to its histological patterns. Furthermore, we elucidated its presence in SCLCs and inflammatory pseudotumors. Also a comparative image was drawn between its expressions in the primary lung tissue and in the metastatic lymph nodes.

Cancer of the corpus uteri.

Cancer of the corpus uteri.

Architectural Versus Nuclear Atypia-defined FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma (EEC)

International Federation of Gynecology and Obstetrics (FIGO) Grade 2 endometrial endometrioid adenocarcinoma carries a 88% 5-yr survival rate. They are defined by >5% but <50% solid epithelial component. A small subset may display <5% solid growth, but marked nuclear atypia and are designated Grade 2. We compared tumor characteristics, staging, and clinical outcome of patients with architectural versus atypia-defined Grade 2 endometrial endometrioid adenocarcinoma. A total of 154 Grade 2 endometrial endometrioid adenocarcinoma cases were reviewed to confirm grade; percent solid growth, and presence of atypia. Only marked atypia (significant nuclear pleomorphism identifiable at 10× or enlarged nuclei, 1.5 to 2× normal, with irregular nuclear contours, dispersed chromatin, and prominent nucleoli) increased the FIGO Grade 1 level. Depth of invasion, tumor stage, lymph node status, and clinical outcomes were then compared. A total of 154 cases were evaluated. Twenty-three were eliminated (6 Grade 3, 17 Grade 1). Of the 131 FIGO II cases, 19 (15%) were based on the presence of severe atypia and 112 (85%) met the architecturally defined criteria. Atypia-defined versus architecturally defined Grade 2 endometrial endometrioid adenocarcinoma's show no significant difference in stage and prognosis. An increase in grade based on presence of nuclear atypia stratifies patients at increased risk as 89% of these patients have myoinvasion at the time of hysterectomy which is in distinct contrast to our previous study (International Journal of Gynecologic Pathology. 2012 July; 31(4): 337-43), where 70% of Grade I cases were noninvasive. No significant correlation between percentage of solid component and risk of recurrence was identified in this study.

BEMS(Building Energy Management System) 구축을 위한 주요 구성요소와 건물에너지효율등급 개선효과에 관한 연구

Currently, the energy consumption rate in buildings is approximately 28.5% of the total energy consumption in Korea. Therefore the amount of the consumption of petroleum resourses is at a worrying level of the blackout. The system of the amount of the Architectural Energy Efficiency Grade [AEEG] is in force by the government to apply the technologies of the Emissions Trading System and the Target Management System to mitigate the Green House Gases for buildings according to the climate change. On the account the mitigation of the Green House Gases and the reduction of the energy, from the view of maintenance and management, for the new and remodeling buildings should be under consideration. The author wants to present the possible ways how to improve the AEEG for<BR>the existing buildings by trying to establish the foundation of the BEMs, and by confirming the potential of the energy savings.