The biological and clinical heterogeneity of younger patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) colorectal cancer (CRC) is largely unexplored. This retrospective study compared the clinicopathological factors, prognosis, and molecular characteristics of MSS/pMMR CRC in patients younger and older than 30 years. Overall, 191 younger (≤ 30 years old) and 892 older (> 30 years old) CRC patients were enrolled. Statistically significant differences between the groups were determined using the χ2 or Fisher’s exact test. Progression-free survival (PFS) was assessed by Kaplan–Meier analysis and compared using log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Younger patients with MSS/pMMR CRC exhibited significantly more aggressive features, including higher rates of mucinous adenocarcinoma, poor differentiation, deeper tumour invasion and advanced tumour–node–metastasis (TNM) stage than older patients. Among all CRC patients, molecular analysis revealed a higher microsatellite instability-high incidence but lower KRAS mutation frequency in younger patients compared with in older individuals. Comprehensive genetic profiling of 1021 genes revealed no additional significant variations between the two MSS/pMMR CRC groups. Survival analysis showed that younger patients with MSS/pMMR CRC had significantly shorter PFS than older patients (log-rank P < 0.001), although multivariate analysis indicated that age was not an independent prognostic factor. Younger patients with CRC exhibit unique biological behaviour. Therefore, unravelling the mechanisms of its aggressiveness through integrated multi-omics technologies should be a key focus in future research.

目的 探讨空芯针穿刺活检对纵隔占位性病变的病理诊断及临床应用价值,分析影响穿刺活检病理诊断准确性的相关因素.方法 回顾性收集2012-2019年河南省肿瘤医院和南京军区总医院共684例纵隔空芯针穿刺活检病例,结合临床病理学特点,评价穿刺活检病理诊断阳性率;与手术切除标本病理诊断或临床最终诊断对比,判断不同种类疾病空芯针穿刺活检的病理诊断准确率,并分析其对纵隔占位性病变病理诊断的敏感度、特异度.结果 本组病例共684例,共穿刺701例次,其中男性448例,女性236例;年龄4～ 84岁;肿物直径1～16 cm;活检病理诊断肿瘤性病变613例,肉芽肿性炎15例,描述性诊断56例;其中76例手术治疗,9例活检和手术结果有偏差,3例具有临床意义;空芯针穿刺活检的病理阳性率为91.8％;组织学类型以胸腺上皮性肿瘤(148例)、癌浸润/转移(144例)、淋巴瘤(119例)和神经内分泌肿瘤(84例)最为多见,活检诊断准确率分别为93.5％、100％、87.8％、98.8％;活检病理诊断的敏感度、特异度分别为97.6％、98.5％.穿刺后22例(3.2％)发生了气胸,症状均较轻微.结论 空芯针穿刺活检对纵隔占位性病变是一种安全有效的诊断方法,具有较高的敏感度和特异度,对癌浸润/转移、神经内分泌肿瘤和胸腺上皮性肿瘤等具有较高的诊断价值,但是淋巴瘤、软组织等部分病例诊断较困难,影响其诊断准确率的关键是足够有效的活检标本量及免疫组织化学和分子检测等的应用.

The prognosis of patients with advanced urothelial carcinoma is dismal. Platinum-based chemotherapy is still the main first-line treatment for advanced urothelial carcinoma, while immunotherapy can be used as a first-line treatment option for people who cannot tolerate platinum. Immunotherapy is preferred in the second-line treatment of bladder urothelial carcinoma. PD-1 inhibitors (Pembrolizumab, nivolumab and atezolizumab) and PD-L1 inhibitors (Ddurvalumab and avelumab) have not been approved for the treatment of advanced urothelial cancer in China. We describe a patient with advanced urothelial carcinoma experienced disease progression after gemcitabine chemotherapy. Following a treatment of domestic PD-1 inhibitor (sintilimab), the patient achieved a durable complete response with mild toxicity. This case indicates that PD-1 inhibitor sintilimab might be a second-line treatment choice for advanced urothelial carcinoma.

目的:探讨转凝蛋白(transgelin,TAGLN)在结直肠癌(colorectal cancer,CRC)组织中的表达及其对SW480细胞增殖、迁移及侵袭的影响.方法:选取郑州大学附属肿瘤医院2015年5月至2016年8月收治的97例CRC患者的癌及配对的癌旁组织标本,以及人CRC细胞系SW620、SW480、HCT116和正常结直肠黏膜细胞株FHC,用免疫组化染色法检测CRC组织中TAGLN的阳性表达率,并分析其表达水平与患者临床病理特征的关系.用qPCR法和WB法分别检测CRC细胞中TAGLNmRNA及蛋白的表达水平.采用脂质体法将si-TAGLN、si-Ctrl转染进SW480细胞,用CCK-8法、划痕愈合实验、Transwell小室法分别检测沉默TAGLN对SW480细胞增殖、迁移及侵袭的影响,用WB法检测EMT相关蛋白上皮型钙黏蛋白(E-cadherin)、神经型钙黏蛋白(N-cadherin)和波形蛋白(vimentin)的表达水平.结果:TAGLN在CRC组织中的阳性表达率明显高于癌旁组织(P＜0.01),其表达水平与CRC患者的TNM分期、肿瘤分化程度和淋巴结转移相关联(P＜0.05或P＜0.01).TAGLNmRNA及蛋白在SW480细胞中的表达水平显著高于FHC细胞(均P＜0.01).沉默TAGLN后,SW480细胞的增殖、迁移及侵袭能力均显著降低(均P＜0.01),细胞中E-cadherin表达水平升高而N-cadherin和vimentin表达水平降低(均P＜0.01).结论:TAGLN在CRC组织和细胞中高表达,沉默TAGLN可抑制CRC细胞的增殖、迁移及侵袭能力,其在CRC的发生发展中起重要作用.

Introduction: Autophagy plays pivotal role in various tumors, including colorectal cancer (CRC). Microsatellite instability (MSI) and KRAS mutations are also involved in response to the adjuvant therapy of CRC. We aimed to investigate the relationships among autophagy, KRAS mutations, MSI, clinicopathological parameters, and prognosis in CRC patients. Methods and Results: We tested 200 CRC tumors for autophagy-related protein expression (Beclin 1 and LC3), MSI status, and KRAS mutations. Results: Expression of Beclin 1 and LC3 was higher in CRC, with Beclin 1 significantly correlating with the depth of invasion, whereas LC3 was not associated with clinicopathological parameters. Patients expressing the LC3 proteins experienced a shorter overall survival (OS) after surgery with adjuvant therapy, especially in the MSS/L-CRC subgroup and the mutated KRAS subgroup. MSS/L-CRC patients with KRAS mutations positively expressed the LC3 protein and suffered a shorter OS than LC3 non-expressing patients. In CRC patients who received either capecitabine or capecitabine combined with oxaliplatin post-surgery, the positive expression of LC3 correlated with worse OS compared to patients who did not express LC3. Sequencing showed BRCA1/2 as the most variant genes in all patients. Nevertheless, deleterious variations were more frequent in patients with MSI-H CRC. Conclusions: High LC3 protein expression shows a certain prognostic value in CRC patients. LC3, the MSI status, and KRAS mutations must be considered when selecting an adjuvant therapy for CRC. The detection of these indexes is of great significance to identify high-risk patients who would benefit from autophagy-related anticancer drugs or help to explore more effective treatment options for patients who are resistant to conventional chemotherapy or relapse.

患者女童,3岁,1年前无明显诱因左前臂突然出现一肿物,约"黄豆"大小,无明显压痛及叩击痛,后肿物缓慢增大.于当地医院就诊行局部肿物切除术,术后病理不详.2个月余前,原手术部位再次出现肿物,当地医院MRI示:左前臂前侧皮下软组织内异常信号,考虑软组织肿瘤,随后来我院就诊.

目的 探讨成涎细胞瘤的临床病理学特征、诊断及鉴别诊断.方法 对1例成涎细胞瘤行HE和免疫组化EnVi-sion两步法染色,分析其临床病理学特征,并复习相关文献.结果 镜下肿瘤主要由基底样上皮细胞组成,被纤细纤维组织分隔,肿瘤细胞呈小导管状、梁状及实性小巢状,周围细胞呈栅栏状排列,瘤细胞胞质少,核圆形或椭圆形,单个或多个小核仁,核染色质细腻,部分区域可见肌上皮细胞;间质疏松、黏液变.免疫表型:肿瘤细胞 CK、CK5/6、CK7均阳性,肌上皮p63、Calponin、S-100均弥漫强阳性,Ki-67增殖指数＜5%.患者术后随访38个月,未见复发或转移.结论 成涎细胞瘤临床罕见,好发于儿童,具有局部侵袭性、复发和转移的特点,确诊需结合病理诊断,治疗以手术切除为主.

Background Our previous study showed that guanine nucleotide exchange factor T (GEFT) was highly expressed in colorectal cancer (CRC) tissues and CRC patients with high GEFT expression had a poor prognosis, and suggested the close link of GEFT expression and CRC tumorigenesis/metastasis. In this text, the roles and upstream regulatory mechanisms of GEFT in the development and progression of CRC were further investigated. Methods Expression levels of GEFT mRNA and LINC00355 was measured by RT-qPCR assay. Protein levels of lin-28 homologue A (LIN28A) and GEFT were determined by western blot assay. Cell proliferative, migratory, and invasive capacities were assessed by CCK-8, Transwell migration and invasion assays, respectively. The effect of GEFT knockdown on CRC tumorigenesis was examined by mouse xenograft experiments in vivo. GEFT mRNA stability was examined by actinomycin D assay. The relationships of LINC000355, LIN28A, and GEFT were explored by RNA pull down and RIP assays. Results GEFT was highly expressed in CRC tissues and cell lines. GEFT knockdown inhibited CRC cell proliferation, migration, and invasion, and hindered CRC xenograft tumor growth. GEFT overexpression alleviated the detrimental effects of LINC00355 loss on CRC cell proliferation, migration, and invasion. LINC00355 promoted GEFT expression and enhanced GEFT mRNA stability via LIN28A. LIN28A knockdown weakened the promotive effect of LINC00355 on CRC cell proliferation, migration, and invasion. Conclusion LINC00355 facilitated CRC tumorigenesis and progression by increasing GEFT expression via LIN28A, deepening our understanding on roles and upstream regulatory mechanisms of GEFT in CRC development and progression.

Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according to the Lauren classification (χ2=12.525, P=0.002) and tumor-node-metastasis (TNM) stages III/IV (χ2=4.033, P=0.045) in GC, and with vessel carcinoma embolus (χ2=7.890, P=0.005) and lymph node metastasis (χ2=5.455, P=0.020) in CRC, but was not associated with other clinicopathological parameters. Patients with high levels of GEFT protein expression had a less favorable outcome compared with patients with low levels of GEFT expression in patients with CRC (χ2=3.876, P=0.049). However, a significant association was not found between GEFT expression and overall survival in patients with ESCC (χ2=0.040, P=0.842) or GC (χ2=0.501, P=0.479). The rate of human epidermal growth factor receptor 2 upregulation in patients with GC was 13.33% and it was associated with nerve invasion (χ2=4.005, P=0.045) and TNM stages III/IV (χ2=5.600, P=0.018). Mismatch repair protein (MMRP) defect was observed in six cases, and the KRAS mutation rate was 26.67% in patients with CRC. GEFT expression was significantly correlated with MMRP (r=-0.285, P=0.027) and KRAS mutation in patients with CRC (r=0.697, P<0.001). These findings revealed frequent GEFT upregulation in malignant digestive tract tumors, which may have promoted tumor development. GEFT expression in CRC may be associated with microsatellite instability and KRAS mutation status, suggesting that GEFT may be a potential therapeutic target for patients with CRC.

隐匿性乳腺癌( occult breast cancer,OBC)为一类少见的特殊类型乳腺癌,发病隐匿,其发病率约占同期乳腺癌的0. 3％～1. 0％[1] ,常给临床诊断和治疗带来困难. 我们收集9例OBC,回顾性分析其临床病理特征和分子分型,旨在提高临床和病理医师对OBC的认识.

口腔颌面部转移性癌为原发身体他处的恶性上皮源性肿瘤转移至口腔颌面部,占该处所有恶性肿瘤 1.0%～2.4%,个别病例以转移灶作为首发症状而就诊,因此需引起重视.本文回顾性分析9例口腔颌面部转移性癌临床病理学特点,旨在提高临床和病理医师对其认识.

嗜酸性黏液表皮样癌(oncocytic mucoepidermoid carcinoma,OMEC)是黏液表皮样癌的一种少见亚型,形态学特征以嗜酸性肿瘤细胞构成为主.我们收集了8例OMEC,结合文献探讨该类病例的病理学特征及组织学起源,旨在提高对这种疾病的认识和诊断的敏感性.