Molecular Characterization of Gastrointestinal Stromal Tumors (Gist) and Contribution of Immunohistochemistry in Congolese from Kinshasa

Introduction: The differentiation of digestive tumors very often requires the use of techniques currently not widely in use in the Democratic Republic of Congo (DRC), such as immunohistochemistry. This is perfectly verified for GISTs whose precise, or at least highly certain, diagnosis can only be made using immunohistochemical markers. This underuse of these techniques due to lack of equipment and human skills explains the limited epidemiological data available to date, thus leading to untargeted and too often late treatment of patients. Research question: What contribution can immunohistochemical markers make to the diagnosis of digestive tract tumours? Objective: Discuss the contribution of immunohistochemical markers in the diagnosis of GIST and provide basic data on the epidemiology of these nosological entities in Kinshasa. Methodology: This was a retrospective study carried out at the LEBOMA private anatomy and pathological cytology centre. The main inclusion criterion was any digestive tract block or slide whose diagnosis of GIST had been requalified after review by at least 2 pathologists. An immuhistochemical study was performed using an automated technique (with a Ventana XT machine) using a panel of antibodies: CD-117 and DOG-1 which are listed in the literature as strongly correlated with the occurrence of GIST, all slides were made at Hj Hospital using an OLYMPUS BX41 co-observation microscope. Results: Of 601 cases of digestive tumors recorded during the concerned period, 32 (5.32%) concerned GIST. This prevalence was confirmed by our immunohistochemical results where the expression of CD117 and that of DOG-1 were positive in 90.6% and 100% of cases which prevalence is high compared with the worldwide prevalence according to the literature, respectively. The distribution of the patients concerned was made with a sex ratio of 1.6 women/men with a median age of 53 years. Most cases (81%) had a gastric location and were fusiform GISTs. Conclusion: Gastrointestinal stromal tumours, although rare and underestimated, account for 5.32% of cases in the DRC. This is a considerable and high prevalence compared with the world average. To the best of our knowledge, no studies have been carried out on these aspects in the DRC, which explains the importance of this study. The results of this research demonstrated the contribution of these 2 markers as specific and effective biomarkers for optimal and differential diagnosis in GIST. In view of the above, it is therefore more than necessary to popularise the use of these biomarkers in order to contribute effectively to improving the overall management of gastrointestinal tumours by improving their identification.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

犬卵巢颗粒细胞瘤的诊断和治疗

犬卵巢颗粒细胞瘤在我国较为罕见。本院接诊了1例因咳嗽、呼吸急促转诊的患犬病例。经实验室检查和影像学检查确诊为卵巢肿瘤并伴有右肺中叶实变、胸腔积液和腹腔积液。肿瘤经手术切除后进一步做组织病理学检查。苏木精-伊红(H.E.)染色结果显示,卵巢组织结构消失,肿瘤细胞形态多样,呈实性片状、索状、小梁状或巢状排列,肿瘤细胞胞质丰富,细胞核呈空泡状,核分裂罕见,可见核仁,染色质粗大;免疫组织化学染色结果显示,卵巢颗粒细胞瘤特异性标记物抑制素-α(INH-α)表达5%阳性,非特异性标记物肾母细胞瘤蛋白1(WT1)和白细胞分化抗原10(CD10)表达阳性。患犬最终确诊为卵巢颗粒细胞瘤,临床分期判定为恶性。该犬在切除肿瘤后第3年复查,状态良好,未见复发,但仍需持续观察。本文旨在对犬卵巢颗粒细胞瘤的诊疗流程进行总结,以供临床参考。

Signif icance of Sentinel Lymph Node Biopsy and Immunohistochemistry in Diagnosis and Staging of Stage-cN0 Oral Squamous Cell Carcinoma

OBJECTIVE To assess the significance of sentinel lymph node biopsy （SLNB）, serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cNO oral squamous cell carcinoma （OSCC）, METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative y-ray probes were used to examine the sentinel nodes in 31 cases with Stage-oNO oral cancer, The H＆E staining and a cytokeratin AE1/ AE3 immunohistochemistry （IHC） assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes, The value of the routine pathological examination of the sentinel lymph node （SLN）, serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised, RESULTS A total of 45, 55 and 51 SLNs were examined in 25 （80%）, 31 （100%） and 30 （96,5%） of the cases, by using the blue stain, y-ray probes, and SPECT lymphoscintigraphy, respectively, The average SLNs found in each case of the groups was 1,4 （1 to 3） and there were 1,302 non-NSLNs, Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non-SLN, One positive SLN metastasis was found after examination of serial sections plus routine H＆E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods, No positive NSLNs were found in the study, CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC （AE1/AE3） methods can be used for examination of the micrometastases which are difficult to identify by routine pathological sections and H＆E staining.

9种犬圆形细胞肿瘤鉴别诊断方法的建立和应用

犬圆形细胞肿瘤(RCT)的鉴别诊断是犬肿瘤病理诊断的难点,且目前犬商用鉴别诊断试剂多为进口,价格高或无购买渠道。为了解决这一难题,本试验选择针对9种犬RCT鉴别诊断的18种免疫标志物抗体和1种特异性染料进行染色分析,并优化染色方法。结果显示,筛选获得组织细胞瘤免疫标志物抗体离子化钙结合适配分子1(Iba 1)、T细胞淋巴瘤免疫标志物抗体白细胞分化抗原3(CD3)、B细胞淋巴瘤免疫标志物抗体白细胞分化抗原20(CD20)、肥大细胞瘤特异性染料甲苯胺蓝(T blue)等13种有效的犬RCT免疫标志物抗体和1种染料;应用优化后的染色方法对临床14例犬RCT病例进行诊断,取得了良好的诊断效果。本试验为犬RCT鉴别诊断提供了经济有效的抗体组合和染色方法。

32例皮肤黑色素瘤临床特点分析

回顾性分析2017年1月至2024年5月我院皮肤科32例皮肤黑色素瘤患者的临床资料。结果示男性发病率为女性的1.46倍;平均发病年龄(69.13±15.95)岁,中位发病年龄为66岁;所有患者均行前哨淋巴结活检,4例淋巴结转移均发生于瘤体>3 cm的患者;SOX10、S-100蛋白、Melan A、HMB45表达阳性率均大于90%;Ki67、Cyclin D1阳性率分别为87.50%、78.13%;Ki67表达水平>5%占比87.50%。

犬髓外浆细胞瘤的组织病理学诊断和免疫组织化学分析

髓外浆细胞瘤(EMP)在犬中属于相对罕见的肿瘤,为了明确犬EMP的组织病理学和免疫标志物表达特征,本试验采用苏木精-伊红(H. E.)染色和刚果红染色法对患犬的皮肤肿物进行组织病理学诊断,进一步使用EMP免疫标志物配对盒基因5(PAX5)、白细胞分化抗原20(CD20)、白细胞分化抗原79a(CD79a)、多发性骨髓瘤基因1(MUM1)和犬免疫球蛋白G(Canine IgG)进行免疫组织化学(IHC)染色,并总结免疫标志物表达特征。结果显示,2例病例的肿物均无包膜结构,并与周围组织边界清晰,肿瘤细胞呈浆细胞样或浆母细胞样特征,病例2肿物内见淀粉样沉积。病例1肿瘤细胞免疫标志物PAX5、CD20和MUM1呈阴性,CD79a和Canine IgG呈阳性;病例2肿瘤细胞免疫标志物PAX5呈阴性,CD20、CD79a、MUM1和Canine IgG呈阳性。结果表明,通过组织病理学检查结合IHC染色结果,确诊2例病例均为犬皮肤型EMP。本试验为犬EMP的精确诊断提供重要的病理学依据,具有重要的参考价值。

Esophageal mesenchymal tumors:Endoscopy,pathology and immunohistochemistry

AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and endoscopic ultrasound （EUS） were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS： Endoscopically, esophageal gastrointestinal stromal tumors （GISTs） and leiomyomas （LMs） had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells： spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcornas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher＇s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 （P 〉 0.05）. All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 （P 〈 0.005）. All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 115 （P 〈 0.005）. CONCLUSION： The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.

Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plasma cells was seen in AIH(90% of cases),PSC(75% of cases),and chronic hepatitis C(100% of cases),while IgMpositive plasma cells predominated in PBC(92.8% ofcases).The IgM /IgG ratio(< 1 or ≥ 1) accurately distinguished PBC from AIH in 90.9% of cases(sensitivity = 92.3%,specificity = 90%),and PBC from either AIH or PSC in 87.8% of cases(sensitivity = 92.3%,specificity = 85.7%).CONCLUSION:Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC,while other forms of liver disease analyzed in this study,including AIH,typically show an IgG-predominant plasma cell infiltrate.Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.

Molecular genetics and immunohistochemistry characterization of uncommon and recently described renal cell carcinomas

Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

Programmed cell death ligand-1(PD-L1) expression by immunohistochemistry: could it be predictive and/or prognostic in non-small cell lung cancer?

Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.

Androgen receptor expression in clinically localized prostate cancer： immunohistochemistry study and literature review

Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.

Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry

Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.

肾细胞癌胃转移一例临床病理分析并文献复习

目的探讨肾细胞癌胃转移的临床特征、病理学形态、免疫组化特点、鉴别诊断,减少误诊。方法回顾性分析1例肾细胞癌孤立性胃转移患者的临床、病理资料,复习国内外相关文献。结果患者男性,71岁,健康查体时胃镜检查显示胃底隆起性病变,病理活检示黏膜层及黏膜下层弥漫巢状、片状增生的肿瘤细胞,细胞形态温和,核小、核膜规则,可见小核仁,胞质透明或嗜酸,间质血管丰富,免疫组化表达CK(pan)、PAX-8、CD10及CAⅨ。追溯病史,患者5年前因透明细胞肾细胞癌行右肾切除,病理诊断为胃转移性透明细胞肾细胞癌。结论肾细胞癌孤立性胃转移非常罕见,细胞形态温和,肾细胞癌的诊断到发现胃转移的平均时间较长,影像学和内镜表现无特殊,因此病理诊断中极易误诊和漏诊。

Comparison of Fluorescence in situ Hybridization and Immunohistochemistry for Assessment of HER-2 Status in Breast Cancer Patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.

Neurofibrillary tangles in Alzheimer＇s disease： elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics

As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.

Significance of immunohistochemistry in breast cancer

The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.

4例犬恶性黑色素瘤病理学和PNL-2免疫组织化学染色检查

为了对4例疑似犬肿瘤的临床病例进行确诊,本文对临床送检的4例疑似犬肿瘤的肿物样本进行组织切片制作,经苏木精-伊红(H.E.)染色后,镜下可见增生的细胞排列呈束状、片状、巢状和螺纹状等,细胞呈梭形或多角形,部分细胞胞浆内含有黑色素颗粒,符合黑色素细胞肿瘤的特征;为了进一步观察细胞形态并对肿物进行确诊,使用黑色素瘤相关抗原(PNL-2)对肿瘤细胞进行免疫组织化学(IHC)染色,并用二氨基联苯胺(DAB)和3-氨基-9-乙基卡唑(AEC)显色液对其显色,结果均为恶性黑色素瘤(MM)。本试验通过对肿物的细胞形态学特征和IHC染色结果综合分析,将4例病例诊断为MM。试验结果不仅为犬MM的病理诊断提供参考,还为比较医学中MM的确诊提供参考依据。

Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.