肺肉瘤样癌14例临床分析

背景与目的 肉瘤样癌（sarcomatoid carcinoma，SC）是一种较少见的癌和肉瘤样形态混合于一个瘤体内的恶性肿瘤。本观察拟探讨肺肉瘤样癌的临床、病理特点。方法 回顾性分析14例经组织病理学证实的肺肉瘤样癌的临床表现、病理特点、治疗经过并进行随访。结果 肺肉瘤样癌发病平均年龄为62岁，男女之比为6比1，临床表现与其他类型肺癌相似。其增强CT有一定特征性，但纤维支气管镜检查难以明确诊断，免疫组化均有上皮表型。结论 肺肉瘤样癌的诊断主要依靠手术病理，不能行手术者可能漏诊，免疫组化对其诊断及鉴别诊断很有帮助。治疗策略与非小细胞肺癌相似。     

Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer

Purpose Cx26, which is a constituent of the connexin family, has recently been shown to promote metastasis through enhancing the vascular invasion in mouse melanoma cells. In this study, we have investigated whether or not Cx26 expression is associated with vascular invasion and recurrences in human breast cancers. Experimental design Cx26 expression was studied in 152 invasive breast cancers by immunohistochemistry. In order to investigate the blood vessel invasion and lymphatic vessel invasion with precision, immunohistochemical staining of blood vessels and lymphatic vessels was carried out using anti-CD34 and anti-D2-40 antibodies, respectively. Results Cx26 was positive in 51.3% (78/152) of the breast tumors. A statistically significant association was observed between Cx26 expression and large tumor size (P = 0.013) or high histological grade (P = 0.043). Frequency of blood vessel invasion was higher in Cx26-positive tumors (5.1%, 4/78) than in Cx26-negative tumors (1.4%, 1/74) though not statistically significant (P = 0.210). Lymphatic vessel invasion was significantly (P = 0.001) more frequent in Cx26-positive tumors (39.7%) than in Cx26-negative tumors (14.9%). Patients with Cx26-positive tumors showed a significantly (P < 0.001) poorer prognosis than those with Cx26-negative tumors. Multivariate analysis showed that Cx26 (P < 0.05) expression was an independent prognostic factor. Conclusions Cx26 expression is associated with lymphatic vessel invasion, large tumor size, high histological grade, and poor prognosis in human breast cancers. Cx26 seems to enhance the metastasis probably through promoting the lymphatic vessel invasion. Cx26 might be clinically useful as a new prognostic factor.     

HLA-F expression is a prognostic factor in patients with non-small-cell lung cancer

Human leukocyte antigens (HLA)-E, -F and -G are referred to as non-classical HLA class I antigens. Among them, the clinical relevance of HLA-E and HLA-G has been intensively investigated, but that of HLA-F remains unknown. In this study, HLA-F expression in 83 primary non-small-cell lung cancer (NSCLC) lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Relevance of HLA-F expression with clinical parameters and patient survival was evaluated. Data revealed that HLA-F expression was observed in 24.1% (20/83) of the NSCLC primary lesions but not in adjacent normal lung tissues. HLA-F expression was not significantly relative to clinicoparameters including patient age, gender, tumor histological type, grade of tumor differentiation and TNM stage. Unexpectedly, patients with HLA-F positive expression had a significantly worse prognosis (p = 0.017). The median overall survival for the patients with HLA-F positive was 10.0 months (range: 4.4-18.3 months) and with HLA-F negative was 17.0 months (range: 10.4-23.6 months), respectively. Multivariate analysis revealed that HLA-F could be an independent prognostic factor with the hazard ratio of 5.12 [95% confidential Intervals (CI): 1.8-14.3]. Summary, this study was for the first time to provide the evidence that HLA-F expression was of clinical significance in tumor patients and that its expression was associated with a poor survival and could be a prognostic indicator in patients with NSCLC.     

Diffuse expression of hRFI is correlated with blood vessel invasion in gastric carcinoma

BACKGROUND: hRFI, which has a relatively high homology to XIAP, is preferentially expressed in esophageal and colorectal carcinomas, and is involved in the initial tumor formation in the colorectal adenoma-carcinoma sequence. Furthermore, its diffuse expression is associated with colorectal carcinogenesis. However, hRFI expression in gastric carcinomas has not been evaluated so far. METHODS: We performed immunohistochemical staining on 76 gastric carcinoma samples using the antibody to hRFI and also analyzed the correlation between the staining pattern of hRFI and the clinico-pathological characteristics. RESULTS: All of the samples were stained focally (31 cases, 40.8%) or diffusely (45 cases, 59.2%) in the cancerous region. On the contrary, most of the normal gastric region showed no staining, except for a few cases that showed slight immunoreactivity in speckles. Furthermore, the proportion of blood vessel involvement was significantly higher in carcinomas with diffuse hRFI expression (28/45, 62.2%) than in carcinomas with focal expression (7/31, 22.6%) (P < 0.001). Liver metastasis was consistently observed in five cases (11.1%) in diffuse, but only one (3.3%) in focal type during the average follow up period of 5 years. However, the 3-year survival rate did not show significant difference between these different staining patterns of hRFI. CONCLUSIONS: These results suggest that the detection of the expression pattern of hRFI in gastric carcinomas can be another useful predictor of liver recurrence, especially when combined with other factors.     

Expression of cysteine-rich 61 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma

Introduction

Cysteine-rich 61 (Cyr61), a secreted protein belonged to the CCN family, was involved in the progression of many cancers. The purpose of this study was to explore the clinical significance of Cyr61 expression in esophageal squamous cell carcinoma (ESCC).

Materials and methods

Cyr61 expression was detected on tissue microarrays of ESCC samples in 372 cases by using immunohistochemical staining. Survival analysis was assessed by the Kaplan-Meier analysis. Relative risk was evaluated by the multivariate Cox proportional hazards model.

Results

The staining pattern of Cyr61 was heterogeneous and varied from negative to intense expression in a cytoplasmic distribution. Kaplan-Meier analysis revealed that expression of Cyr61 was related to poor survival of ESCC patients (P = 0.001). Further analysis revealed that Cyr61 high-expression was related to poorer overall survival of patients in stage I/II (P = 0.001); but did not effect the overall survival of patients in stage III/IV. Univariate and multivariate analysis suggested that Cyr61 expression status was an independent prognostic factor for ESCC (P = 0.001).

Discussion

Cyr61 might play important roles in the progression of ESCC. Cyr61 is a new biomarker to predict the prognosis of ESCC patients.     

肉瘤样肝细胞癌中MET基因扩增与预后的相关性分析

背景与目的：肉瘤样肝细胞癌（sarcomatoid hepatocellular carcinoma,SHC）是一种罕见且高度恶性的肝脏肿瘤。MET基因异常具有肿瘤预后预测价值,以MET为靶点的抑制剂已成为晚期肿瘤治疗的重要方向,然而SHC组织中MET基因扩增状态尚不明确。探讨SHC中MET基因扩增与临床病理学因素的相关性及其预后预测价值。方法：收集2008年1月—2016年12月于复旦大学附属中山医院经病理学检查确诊的22例SHC患者资料。采用荧光原位杂交（fluorescence in situ hybridization,FISH）法检测上述患者的MET基因扩增情况,并结合临床病理学资料进行统计学分析。采用Kaplan-Meier模型分析总生存期（overall survival,OS）及无病生存期（disease-free survival,DFS）,采用log-rank检验比较生存曲线,采用多因素COX回归模型分析SHC中独立的预后因素。结果：22例SHC患者中,MET基因扩增5例（22.7%）。MET基因扩增存在异质性,主要位于分化差的梭形细胞区域（4例）。MET基因扩增的SHC患者中位OS明显短于MET阴性患者（6.8个月 vs 24.0个月,P=0.001）。SHC中具有完整肿瘤包膜的患者中位OS明显长于包膜不完整的患者（41.3个月 vs 8.5个月,P=0.001）。单灶肿瘤及中国肝癌分期（China Liver Cancer Staging,CNLC）Ⅰ期患者的中位DFS较多灶肿瘤及Ⅱ+Ⅲ+Ⅳ期患者明显延长（10.4个月 vs 3.8个月,12.4个月 vs 3.8个月,P=0.027和0.017）。MET基因扩增是SHC独立的预后因子。结论：22.7%（5/22）的SHC中存在MET基因扩增。MET基因扩增的SHC患者预后更差,是其预后的独立危险因素。该研究结果为该罕见肿瘤的治疗提供了新策略和临床依据。     

脏层胸膜侵犯和脉管癌栓对非小细胞肺癌术后初始复发部位及预后的影响

背景与目的：脏层胸膜侵犯(visceral pleural invasion,VPI)和脉管癌栓(vessel invasion,VI)是非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后的危险因素,前者的初始复发部位可能以局部复发为主,而后者可能以远处转移多见。本研究主要探讨VPI和VI对初始复发部位及术后生存率的影响。方法：回顾性分析广西医科大学附属肿瘤医院2007年1月—2013年12月期间住院的NSCLC手术治疗患者的完整资料共计290例。VPI患者51例,无VPI患者239例;有VI患者29例,无VI患者261例,分别比较其临床特征、总生存期(overall survival,OS)及无病生存期(disease-free survival,DFS)的差异。结果：VPI组与无VPI组的肿瘤大小、淋巴结转移、TNM病理分期和初始复发部位相比,差异有统计学意义(P<0.05)。VI组与无VI组的淋巴结转移和TNM病理分期相比,差异有统计学意义(P<0.05)。VPI组的1年、3年和5年生存率(88.2%、56.7%和52.7%)均低于无VPI组(95.8%、83.7%和74.0%),差异有统计学意义(P<0.001)。VI组的1年、3年和5年生存率(79.3%、56.8%和48.7%)均低于无VI组(96.1%、81.3%和72.3%),差异有统计学意义(P=0.001)。Cox多因素分析结果显示,TNM病理分期是患者DFS的独立影响因素(P<0.05)。淋巴结转移、VPI是患者OS的独立影响因素(P<0.05)。结论：VPI患者的初始复发部位以局部复发多见;VPI和VI的NSCLC患者预后均较差,需要更积极的术后治疗。     

嗜神经侵袭阳性鼻腔副鼻窦腺样囊性癌的治疗及预后分析

目的分析嗜神经侵袭(PNI)阳性鼻腔副鼻窦腺样囊性癌(ACC)的疗效, 探讨PNI在鼻腔副鼻窦ACC中的预后价值。方法回顾性分析2000年1月至2016年12月中国医学科学院肿瘤医院收治的105例鼻腔副鼻窦ACC患者的临床资料。按照美国癌症联合委员会和国际抗癌联盟第8版分期系统重新分期。随访获取患者治疗失败和生存资料, 预后影响因素的单因素分析采用Log rank检验, 多因素分析采用Cox回归比例风险模型。结果上颌窦(59例)为最常见的肿瘤原发部位, 其次为鼻腔(38例)。Ⅲ～Ⅳ期患者93例。治疗方式包括单纯手术14例, 单纯放疗13例, 术前放疗+手术10例, 手术+术后放疗68例。中位随访91.8个月, 5年局部控制率、无远处转移生存率、无进展生存率和总生存率分别为72.6%、73.0%、52.9%和78.0%。33例(31.4%)患者PNI阳性, 其5年无远处转移生存率、无进展生存率和总生存率分别为53.7%、29.4%和56.5%, 均低于PNI阴性组(分别为80.8%、63.0%和86.8%, 均P<0.05), 而两组的局部控制率差异无统计学意义(64.5%和76....     

Prognostic significance of blood vessel invasion in carcinoma of the breast in women

Prognostic significance of blood vessel invasion in carcinoma of the female breast has been evaluated by study of 242 cases of radical mastectomy done at the Tata Memorial Hospital. The significance of axillary node involvement with the disease has been simultaneously evaluated. In the absence of blood vessel invasion and lymph node metastasis the 5 year survival rate was 98%. Compared with this, 5 year survival rate was reduced to 59% when the blood vessel invasion was present but no lymph node metastasis. Only 12% survived for 5 years when both blood vessels and lymph nodes were involved with the disease. The study indicated that blood vessel invasion in the primary breast carcinoma is more significant than lymph node metastasis.     

Expression of fibroblast growth factor 9 is associated with poor prognosis in patients with resected non-small cell lung cancer

Objectives

Fibroblast growth factor (FGF) 9 is a member of the FGF family, which modulates cell proliferation, differentiation, and motility. Recent studies show that the activation of FGF signals including FGF9 is associated with the pathogenesis of several cancers; however, its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to clarify the characteristics of NSCLC with FGF9 expression.

Materials and Methods

We evaluated the expression of FGF9 in resected NSCLC specimens and corresponding non-tumorous lung tissue samples using cDNA microarray and evaluated its clinicopathological characteristics.

Results

Nine out of 90 NSCLC specimens (10%) had “high” FGF9 expression compared with corresponding non-cancerous lung tissues. Histologically, of the 9 NSCLC specimens with high FGF9 expression, 5 were adenocarcinoma, whereas none were squamous cell carcinoma. FGF9 expression was not associated with sex, smoking history, or clinical stage. However, in patients with high and low FGF9 expression, the postoperative recurrence rates were 78% and 24% (p = 0.033), respectively. Overall survival was significantly shorter in patients with high FGF9 expression than in those with low FGF9 expression (p < 0.001).

Conclusion

Our data indicate that FGF9 may be a novel unfavorable prognostic indicator and a candidate therapeutic target of NSCLC.     

Differences in the prognostic implications of vascular invasion between lung adenocarcinoma and squamous cell carcinoma

Objectives

Vascular invasion (VI) has been accepted as a universally important prognostic factor for patients with lung carcinoma. However, the clinical significance of VI in each of the histological subtypes has been unclear. The aim of the present study was to investigate differences in the clinicopathological implications of VI between adenocarcinoma and squamous cell carcinoma.

Method

A total of 336 patients were evaluated, of whom 81 were diagnosed as having peripheral-type squamous cell carcinoma, and 255 as having adenocarcinoma.

Result

Among the 336 patients, the five-year survival rates for those who were VI-positive and VI-negative were 38.4% and 76.3%, respectively, the difference being significant (p < 0.0001). Multivariate analysis identified VI as an independent prognostic factor (hazard ratio: 1.86). Although the difference in cancer-free survival between VI-positive and -negative patients was statistically significant for adenocarcinoma (p < 0.0001), it was not significant for squamous cell carcinoma (p = 0.086). For adenocarcinoma, the difference between the survival curves for VI-positive and -negative patients was significant for the subtypes with a predominant lepidic (p < 0.0001), papillary (p = 0.0026), and acinar (p = 0.0060) component, whereas that for the predominantly solid subtype was not significant (p = 0.58). Squamous cell carcinomas were then divided into two groups on the basis of the diameter of vessels that had been invaded by the cancer cells: large-vessel invasion (LVI; 1000 μm or more) and small-vessel invasion (SVI; less than 1000 μm). Although there was no difference in the survival curves between the LVI and SVI groups, the LVI group showed a significantly higher incidence of cavity formation and distant metastasis.

Conclusion

We conclude that VI is a useful prognostic indicator in lung carcinoma, although the clinical implications of VI differ between adenocarcinoma and squamous cell carcinoma.     

五例肺肉瘤样癌的临床病理和影像学特点

肺肉瘤样癌(pulmonary sarcomatoid carcinoma,PSC)是肺部极少见的恶性肿瘤,我院心胸外科共收治5例PSC患者,均经病理检查证实.结合相关文献,我们对PSC的临床、病理和影像学特点进行综合分析,现将结果报告如下.     

微血管侵犯对肝癌肝移植患者预后的影响

目的探讨微血管侵犯(MVI)对肝细胞癌肝移植患者总生存时间(OS)和无复发生存时间(RFS)的影响。方法收集2004年5月至2017年10月接受肝移植术的肝癌患者的临床病理资料。采用Kaplan-Meier法和Cox比例风险模型分析MVI对OS和RFS的影响。结果共纳入141例肝癌肝移植患者,其中54例(38.3%)MVI阳性,87例(61.7%)MVI阴性。与MVI阴性患者比较,MVI阳性患者具有更高的甲胎蛋白(AFP)和血小板水平,更高的中性粒细胞-淋巴细胞计数比值,更大的肿瘤直径,更高比例的卫星灶、低分化肿瘤和超米兰标准病例(P<0.05)。随访截止于2020年1月15日,55例(39.0%)肿瘤复发,56例(39.7%)死亡。MVI阳性患者1、3、5、10年无复发生存率分别为48.1%、36.5%、36.5%和19.0%,低于MVI阴性患者的85.1%、76.8%、71.9%和60.0%(P<0.001)。MVI阳性患者1、3、5、10年生存率分别为77.8%、42.3%、42.3%和23.3%,低于MVI阴性患者的94.3%、83.6%、77.2%和68.4%(P<0.001)。Cox多因素分析显示,MVI、AFP水平、肿瘤直径和肿瘤数目是影响肝癌肝移植患者RFS和OS的独立因素。结论MVI对肝癌肝移植患者的预后具有显著影响,MVI侵犯的患者预后不良。     

脏层胸膜受侵对Ⅰb期非小细胞肺癌预后的影响

目的 探讨脏层胸膜受侵对Ⅰ b期非小细胞肺癌预后的影响.方法 回顾性分析1994年1月至2003年12月间在我院接受手术切除的232例Ⅰ b期非小细胞肺癌(NSCLC)患者的临床和随访资料.根据肿瘤大小和脏层胸膜受侵情况,将患者分为3组,A组:肿瘤最大径＞3 cm且无脏层胸膜受侵;B组:肿瘤最大径≤3 cm且脏层胸膜受侵;C组:肿瘤最大径＞3 cm且脏层胸膜受侵.运用Kaplan-Meier生存分析和Cox比例风险模型,对影响NSCLC预后的因素进行分析.结果 A组45例,B组96例,C组91例,其5年生存率分别为70.1%、61.9%和56.2%,10年生存率分别为56.7%、50.6%和35.9%,3组生存率之间的差异有统计学意义(P＝0.018).脏层胸膜受侵者187例(80.6%), 5年和10年生存率分别为59.3%和42.6%;无脏层胸膜受侵者45例(19.4%), 5年和10年生存率分别为70.1%和56.7%,两组生存率之间的差异有统计学意义(P＝0.035).多因素分析显示,以肿瘤大小和脏层胸膜受侵情况分组为变量,是影响预后的因素(RR＝1.530,95%CI为1.132～2.067,P＝0.006).结论 Ⅰ b期NSCLC中,不同T状态患者生存率之间的差异有统计学意义,肿瘤最大径＞3 cm且脏层胸膜受侵的患者预后较差,这一T2状态是否需要修改有待进一步的研究.     

Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study

Recently, peritumoural (lympho)vascular invasion, assessed on haematoxylin-eosin (HE)-stained slides, was added to the St Gallen criteria for adjuvant treatment of patients with operable breast cancer (BC). New lymphatic endothelium-specific markers, such as D2-40, make it possible to distinguish between blood (BVI) and lymph vessel invasion (LVI). The aim of this prospective study was to quantify and compare BVI and LVI in a consecutive series of patients with BC. Three consecutive sections of all formalin-fixed paraffin-embedded tissue blocks of 95 BC resection specimens were (immuno)histochemically stained in a fixed order: HE, anti-CD34 (pan-endothelium) and anti-D2-40 (lymphatic endothelium) antibodies. All vessels with vascular invasion were marked and relocated on the corresponding slides. Vascular invasion was assigned LVI (CD34 [plus sign in circle] or [minus sign in circle]/D2-40 [plus sign in circle]) or BVI (CD34 [plus sign in circle]/D2-40 [minus sign in circle]) and intra- (contact with tumour cells or desmoplastic stroma) or peritumoural. The number of vessels with LVI and BVI as well as the number of tumour cells per embolus were counted. Results were correlated with clinico-pathological variables. Sixty-six (69.5%) and 36 (37.9%) patients had, respectively, LVI and BVI. The presence of 'vascular' invasion was missed on HE in 20% (peritumourally) and 65% (intratumourally) of cases. Although LVI and BVI were associated intratumourally (P=0.02), only peritumoural LVI, and not BVI, was associated with the presence of lymph node (LN) metastases (p(peri)=0.002). In multivariate analysis, peritumoural LVI was the only independent determinant of LN metastases. Furthermore, the number of vessels with LVI was larger than the number of vessels with BVI (P=0.001) and lymphatic emboli were larger than blood vessel emboli (P=0.004). We demonstrate that it is possible to distinguish between BVI and LVI in BC specimens using specific lymphatic endothelium markers. This is important to study the contribution of both processes to BC metastasis. Furthermore, immunohistochemical detection of lymphovascular invasion might be of value in clinical practice.     

Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung

The purpose of this study was to investigate the possible association between expression of survivin, pathological findings in the tumor and survival in patients with small adenocarcinoma of the lung. Seventy-nine patients with resected tumors <2 cm in diameter were entered into the study. There were 33 males and 46 females, with a median age of 64 years (range 26-83 years). The pathological stage of the tumors was recorded as stage I, II, III and IV in 72, one, five and one case, respectively. Each patient underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for survivin. Thirty-eight patients had tumors with < or = 10% survivin-positive cells and 41 patients had tumors with >10% survivin-positive cells. When survivin expression and pathological findings in the resected tumors were analyzed, the frequency of venous invasion was significantly higher in the survivin-positive group (36.6% vs. 13.2%; p=0.0167). In contrast, the overall survival of survivin-positive patients (n=41) was significantly worse than that of individuals whose tumors were negative for survivin expression (n=38; log-rank test, p=0.014; Wilcoxon test, p=0.021). It can be concluded that the expression of survivin in tumor cells is a factor of poor prognosis in patients with small adenocarcinoma of the lung.     

p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung

An immunohistochemical analysis for p16 protein was performed in 171 patients with non-small-cell lung cancer (NSCLC). Sixty-two carcinomas (36.3%) were classified as p16-negative. p16-negative tumours in squamous cell carcinomas (SCCs) were significantly more than those in adenocarcinomas (P = 0.039). There was no significant difference in survival according to tumour p16 status in patients with NSCLCs or in patients with adenocarcinomas. In contrast, of patients with SCCs, the 5-year survival rate of patients with p16-negative tumours was significantly lower than those with p16-positive tumours (P = 0.001). Especially, the survival of patients with p16-negative tumours was significantly worse than that of patients with p16-positive tumours in the early stage of the SCC, e.g. stage I (P = 0.005). Multivariate analysis showed that p16 status and nodal status were significant prognostic factors for the survival of patients with SCCs of the lung (P = 0.024 and P = 0.008 respectively). In conclusion, our study showed that alteration of p16 was one of the significant factors of a poor prognosis in SCCs of the lung, and that p16 might play an important role in some SCCs of the lung due to its high prevalence and prognostic value.