Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma

Bovio I M, Al‐Quran S Z, Rosser C J, Algood C B, Drew P A & Allan R W
(2010) Histopathology 56, 951–956
Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma Aims: To prospectively evaluate the utility of smoothelin immunohistochemical expression for the evaluation of muscularis propria (MP) in diagnostic transurethral resection of bladder tumour (TURBT) specimens and cystectomies. Methods and results: Smoothelin immunohistochemistry was performed on a total of 26 TURBT and cystectomy specimens. All but two cases (24/26) demonstrated strong (3+) or moderate (2+) immunoreactivity of the MP with smoothelin. Muscularis mucosae (MM) never displayed strong (3+) reactivity, and in only one case did the MM have moderate (2+) reactivity; in this case the MP had strong (3+) reactivity. MM intensity mirrored the intensity of reactivity of blood vessels in all cases (26/26). Using moderate or strong immunoreactivity as a cut‐off, smoothelin had a sensitivity of 92% for detecting MP and a specificity of 97% for distinguishing between MP and MM. In all unequivocal MP‐invasive and lamina proporia‐invasive cases by haematoxylin and eosin (H&E), smoothelin immunohistochemistry confirmed the original light microscopic diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. Conclusions: Smoothelin immunohistochemistry has diagnostic utility in the evaluation of MP invasion in urothelial carcinoma. Smoothelin could be used as an adjunct to traditional H&E‐stained light microscopy and may help reduce the number of equivocal diagnoses.     

Neurovascular alterations of muscularis propria in the human anterior vaginal wall in pelvic organ prolapse

In the pathophysiology and progression of pelvic organ prolapse (POP), it has been demonstrated that there is a reorganisation of the muscularis propria of the anterior vaginal wall due to a phenotypic smooth muscle cell to myofibroblast switch. An abnormal deposition of collagen type III seems to be influenced by the involvement of advanced glycation end‐products. The aim of the present study was to evaluate the hypothesis that this connective tissue remodelling could also be associated with neurovascular alterations of the muscularis in women with POP compared with control patients. We examined 30 women with POP and 10 control patients treated for uterine fibromatosis. Immunohistochemical analysis, using glial fibrillary acidic protein, S‐100 protein, receptor tyrosine kinase, neurofilament and α‐smooth muscle actin antibodies, was performed. S‐100, receptor tyrosine kinase and neurofilament were also evaluated using Western blot analysis. We observed a decrease in all neurovascular‐tested markers in nerve bundles, ganglia and interstitial cells of Cajal from POP samples as compared with controls. Even if the processes responsible for these morphological alterations are still not known, it is conceivable that collagen III deposition in the anterior vaginal wall affects not only the architecture of the muscle layer but could also modify the intramuscular neurovascularisation and account for an alteration of the neuromuscular plasticity of the layer.     

Natural killing activity is associated with progression of gastric cancer

Previously, we proposed a new analysis of natural killing activity, in which an individual effector/target cell ratio was employed for comparison according to the peripheral number of effector cells. In 51 patients with gastric cancer, the activity was studied using that modified analysis. Natural killing activity was activated in patients with early cancer, where tumor-cell invasion was restricted to the mucosa or the submucosa, even though in well-differentiated adenocarcinoma with invasion of the mucosa alone, the activity remained at the level of controls. In contrast, the activity in advanced cancer, where tumor cells infiltrated beyond the submucosa, came to be inactivated as the cancer progressed. These facts suggest that natural killing activity in patients with gastric cancer is closely associated with tumor invasion and that reactive activation of the activity against tumor is induced, at least, in some patients with early stage.     

内镜经黏膜下隧道肿瘤切除术治疗食管胃接合处固有肌层来源的黏膜下肿瘤

目的 探讨内镜经黏膜下隧道肿瘤切除术(STER)在食管胃接合处(EGJ)固有肌层来源的黏膜下肿瘤(SMTs)治疗中的有效性及安全性。方法 回顾性分析2013年10月—2015年10月滨海县人民医院消化内科46例EGJ固有肌层来源的SMTs患者的临床资料,其中男25例、女21例,年龄34~69(46.3±12.7)岁;肿瘤直径1.2~3.0 cm,中位直径2.1 cm。46例患者均行STER治疗,手术切除标本均经病理学检查明确诊断;术后观察患者手术并发症发生情况,并随访疗效。结果 肿瘤完整切除率为100%。46例中,平滑肌瘤26例、胃肠间质瘤20例,切缘均阴性;手术时间42~125 min,中位时间85 min。术后7例发生少量皮下气肿伴气胸,未予特殊处理,保守治疗后痊愈;未发生迟发性出血、继发性感染及消化道瘘等并发症。46例均获随访,中位随访时间为8个月(1~24个月),无局部复发或转移者,无一例患者死亡。结论 采用STER治疗EGJ固有肌层来源的SMTs,短期疗效好、并发症少,术式安全有效。     

The prevalence and character of the muscularis mucosae of the human urinary bladder

We report the results of a histological evaluation of 335 consecutive autopsy specimens of apparently normal urinary bladder for the presence of a complete, partial or minimal muscularis mucosae. There were 164 females (49%) and 171 males (51%), ranging in age from 20 weeks of gestation to 102 years. A muscularis mucosae was present in 117 bladders (35%). The female to male ratio was 2:1, with 45% of female and 25% of male bladders containing a muscularis mucosae. The muscularis mucosae was complete in one case (1%), partial in 23 cases (6%) and minimal in 93 cases (28%). The occurrence of a partial or complete muscularis mucosae was ten times more likely in women than men. The presence of a muscularis mucosae in both women and men was not associated with any known disease process, nor was it related to patient age.     

Predicting lymph node status in patients with early gastric carcinoma using double contrast-enhanced ultrasonography

Introduction

Double contrast-enhanced ultrasonography (DCUS) is a new method we used in predicting lymph node metastasis (LNM) in patients with early gastric cancer.

Material and methods

Seventy-six patients with early gastric cancer diagnosed by gastroscope and confirmed by pathology after operation were examined using DCUS preoperatively. Group N1 included 15 patients with LNM and group N0 61 patients without LNM.

Results

In group N1, 13 patients (87%) had marked hyperenhancement during early arterial phase using DCUS, and 2 patients (13%) were unmarked as hyperenhancement. In group N0, 24 patients (39%) had marked hyperenhancement during early arterial phase using DCUS, and 37 patients (61%) had unmarked hyperenhancement. The sensitivity and specificity of marked hyperenhancement in predicting LNM in patients with early gastric cancer was 86.7% and 60.7% respectively, and the Youden’s index was 0.474. The κ value of this method was 0.89.

Conclusions

Double contrast-enhanced ultrasonography is a new valuable method to evaluate LNM at an early stage of gastric cancer and prognosis of early gastric cancer preoperatively.     

Retrospective studies of early gastric cancer in a high incidence area of Italy

Frequency and characteristics of early gastric cancer (egc) were evaluated in a retrospective study of 511 surgical specimens of gastric carcinoma. We observed a total of 46 egc in 40 patients. The predominant macroscopic type was IIc, followed by I and III. On the basis of histological appearance, 25 egc were of intestinal type and 15 of diffuse type. Seventy-six per cent of egc were localized at the lesser curvature of the stomach and in particular at the pyloric antrum. Twenty-two egc were limited to the mucosal layer. No relationship was observed between macroscopic type or histological characters, and tumour staging. As Italy can be considered a high-risk country for gastric carcinoma and because this disease is in many respects similar to that observed in Japan, it seems possible to obtain a reduction of the death rate for gastric cancer by increasing, as in Japan, the number of cancers diagnosed in the early phase.     

Familial gastric carcinoma

Most cases of gastric cancer are sporadic and familial clustering is observed in about 10% of cases. Hereditary gastric cancer accounts for a very low percentage of cases (1–3%), encompassing: hereditary diffuse gastric cancer (HDGC) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Furthermore, gastric cancer can develop in the setting of other hereditary cancer syndromes such as Li–Fraumeni syndrome, Familial Adenomatous Polyposis, Peutz–Jeghers syndrome, Lynch syndrome, MUTYH-associated adenomatous polyposis, Juvenile Polyposis syndrome, and Cowden syndrome. HDGC is caused by alterations of the CDH1 gene that encodes for e-cadherin and the model of development encompasses non-atrophic gastritis, in situ signet ring cell carcinoma, pagetoid spread of signet ring cells and invasive carcinoma. GAPPS is characterized by proximal fundic gland polyposis, with areas of dysplasia or intestinal-type gastric cancer, without evidence of colorectal polyposis or other heritable gastrointestinal cancer syndromes. The genetic cause of GAPPS has not been identified yet.     

Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log-rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Adenocarcinoma of the stomach with invasion limited to the muscularis propria

Adenocarcinoma of the stomach having invasion limited to the muscularis propria with or without lymph node metastasis, termed PM (proper muscle) gastric cancer by Japanese investigators, has a prognosis superior to that of carcinoma extending to the serosa and approaching that of early gastric cancer in Japan. To evaluate the occurrence and significance of PM gastric cancer in the United States, we analyzed 272 gastric carcinomas resected at our institution between 1964 and 1983. Forty-two PM cancers (15%) were identified. Improved 5-year survival rate was noted for PM cancer when compared with survival rate for 215 neoplasms exhibiting serosal invasion (29% versus 7%, P less than 0.001). In univariate analysis, a survival advantage was also associated with absence of lymph node metastasis, intestinal-type histopathology of the Lauren classification, the expanding pattern of the Ming classification, and polypoid or fungating gross configuration of tumor. In multivariate analysis, depth of tumor invasion remained significantly associated with improved 5-year survival rate independently of other variables, including lymph node metastasis. Using continuous survival curves, the prognostic significance of PM cancer prevailed throughout the 5-year postgastrectomy interval. Our data indicate that PM gastric cancer occurs in the United States and need not be considered "advanced" gastric carcinoma; depth of tumor invasion should be recognized as a nodal metastasis-independent prognosticator of gastric cancer survival.     

早期胃癌临床诊治的若干问题

胃癌是全球范围内死亡率最高的恶性肿瘤之一,而胃癌的早期发现和规范化治疗是改善胃癌患者的重要手段。随着医疗技术的发展,早期胃癌的检出率逐年提高,并且手术方式逐渐从传统开腹根治术向内镜切除和腹腔镜手术过渡。本课题组通过多年系列研究,联合国内外最新发现对早期胃癌临床生物学特征、分期系统评估和综合治疗方案等方面进行深入研究,为指导早期胃癌临床诊治提供科学依据。     

幽门螺杆菌感染与胃黏膜增殖及与胃癌预后的关系

目的 :探讨增殖细胞核抗原 (PCNA)在幽门螺杆菌 (HP)感染的不同胃黏膜增殖性病变演进中的表达情况及其相互关系 ,并着重探讨HP感染对胃癌预后的意义。方法 :对 14 5例经病理证实的不同胃黏膜病变用免疫组化方法检测PCNA标记指数 (LI) ,Warthin Starry(W S)法检测HP感染。结果 :在浅表性胃炎 (CSG)、萎缩肠化性胃炎 (CAG +IM)、异型增生 (DYS)、早期胃癌和进展期胃癌中 ,PCNA LI为 2 4 0 0± 17 88,4 6 5 9± 18 15 ,6 0 5 9± 2 0 2 6 ,5 7 92± 15 15 ,71 0 8± 2 1 2 5。在IM、DYS、胃癌组织均高于CSG(P <0 0 5 )。PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关 ,而且Bor rmannIV高于早期胃癌 (P <0 0 5 )。PCNA阳性表达与肠型胃癌HP感染有关。CAG +IM、DYS和GC组PCNA阳性表达中HP感染者高于阴性者。胃癌HP阳性者 5年存期短于HP阴性者。结论 :PCNA基因表达与胃黏膜增殖和恶化有关。HP感染和胃黏膜增殖和恶化有关 ,HP感染与胃癌预后有关。     

Implication of Reprimo and hMLH1 gene methylation in early diagnosis of gastric carcinoma

DNA methylation has been recently recognized as a novel tumor marker. This study investigated the methylation status of Reprimo and hMLH1 gene in both plasma and tissue samples from gastric cancer patients, in an attempt to investigate their diagnostic implications in gastric cancer. A total of 180 tissue and plasma samples (including 50 cases of gastric cancer, 50 dysplasia, 50 chronic atrophic gastritis with intestinal metaplasia and 30 normal controls) were collected for detecting DNA methylation status of Reprimo and hMLH1 genes using MSP method. Tissue protein expression levels were further tested by immunohistochemical (IHC) staining. The positive rate of DNA methylation rate was, in ascending sequence, gastritis tissue, dysplasia tissue and gastric carcinoma tissue. All those tissues had significantly elevated DNA methylation level compared to normal group (P < 0.05). Expression level of Reprimo and hMLH1 proteins were, however, decreased in pathological tissues compared to normal ones (P < 0.05). A significantly negative relationship existed between protein level and promoter region methylation level. The DNA methylation occurred in promoter regions of both Reprimo and hMLH1 genes depressed the protein expression, and may participate in the occurrence and progression and gastric cancer. The combined assay of serum Reprimo and hMLH1 DNA methylation levels thus had critical importance in the early diagnosis and gastric cancer.     

Erythropoietin as an angiogenic factor in gastric carcinoma

AIMS: Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo-R) expression in endothelial and tumour cells with histopathological type in gastric cancer. METHODS AND RESULTS: Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 and anti-Epo-R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo-R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis. CONCLUSIONS: Epo-R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti-angiogenic therapy in patients with gastric cancer.     

基层医院56例早期胃癌胃镜下表现的分析

目的探讨早期胃癌(EGC)普通胃镜下的表现,为提高基层医院EGC的检出率提供参考。方法回顾性分析我院确诊的早期胃癌56例患者的内镜下表现,包括发生部位、大小、分型及各型表现以及亚甲蓝着色特征。结果 56例患者中,病灶位于胃窦部22例(39.3%),胃体部18例(32.1%),胃角部10例(17.9%),贲门部6例(10.7%)。单个病灶直径为0.5~2.6 cm,平均(1.28±1.36)cm。Ⅰ型(隆起型)12例(21.4%),Ⅱ型(平坦型)36例(64.3%),其中Ⅱa型(浅表隆起型)10例(17.9%),Ⅱb型(浅表平坦型)2例(3.6%),Ⅱc型(浅表凹陷型)24例(42.9%),Ⅲ型(溃疡型)2例(3.6%)。56例患者经亚甲蓝染色后,病变黏膜呈黑色或深蓝色48例(85.7%),浅蓝色6例(10.7%),不着色2例(3.6%)。结论 EGC好发于胃窦部,以Ⅱc型为主,多数病变亚甲蓝染色呈深蓝色。     

早期胃癌规范化诊治流程及预后因素

胃癌依然是世界范围内最常见的癌症之一。近些年,在日本,早期胃癌(early gastric cancer,EGC)约占胃癌治疗患者的57%,而在中国,该比例却不足10%。包括内镜粘膜下剥离术(endoscopic submucosal dissection,ESD)和内镜下粘膜切除术(endoscopic mucosal resection,EMR)在内的微创手术,对于EGC患者而言是治愈性的治疗,而且患者会获得很好的预后。对于EGC而言,规范化诊治流程非常重要。首先,内镜、超声内镜及组织学检查是筛选微创手术患者的关键步骤。第二,仔细评估微创手术标本可以为将来可能的外科干预提供重要信息,这些信息包括脉管瘤栓、肿瘤体积、组织学类型、浸润深度。此外,淋巴细胞浸润情况,淋巴管侵犯、HER2/neu、Mucin-4、VEGF C、VEGF D过表达是EGC的预后因素。     

Intramucosal cysts in gastric mucosa adjacent to carcinoma and peptic ulcer: a histochemical study

Histochemical characteristics and the distribution of gastric intramucosal cysts were studied in 50 cancerous and 51 benign gastrectomy specimens. The frequency of such cysts was significantly higher in stomachs with carcinoma (70%) than in stomachs with peptic ulcer (43%) (P less than 0.01). Intramucosal cysts were classified into gastric type, small intestinal type, colonic type and non-mucous type. There were significant differences in the constituent ratios of the four types of cyst between gastric carcinoma and gastric ulcer (P less than 0.01), as well as between intestinal type and diffuse type cancer (P less than 0.001). The present results reveal a close relationship between intramucosal cysts and gastric carcinoma. Cysts of small intestinal, colonic and non-mucous types were associated with intestinal type cancer while cysts of gastric type were related to diffuse type cancer of the stomach.