Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma

BackgroundPatients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma.MethodsWe retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018 at our institution for information on the recurrence of the disease.ResultsPer the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42–36.2, P = 0.0012; and OR: 4.50, 95% CI: 1.52–13.4, P = 0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08–42.5, P = 0.0003).ConclusionsThe presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.     

肿瘤相关巨噬细胞在乳腺浸润性微乳头状癌中的浸润及意义

目的 研究肿瘤相关巨噬细胞（tumor associated macrophages,TAMs）在乳腺浸润性微乳头状癌（invasive micropapillary carcinoma,IMPC）中的浸润及意义.方法 采用免疫组织化学链霉亲和素生物素法（laballad streptavidin biotin method,LSAB）检测68例IMPC和72例浸润性导管癌非特殊型（invasive ductal carcinoma,not otherwise specified,IDC-NOS）中TAMs标记物CD68、CD163的表达,并探讨其与临床病理学特征的关系.结果 CD68、CD163主要表达于IMPC及IDC-NOS间质中浸润的巨噬细胞的胞膜或胞质内,癌巢内偶有表达.IMPC组瘤内间质CD68的表达率（47/68,69.1％）明显高于IDC-NOS组（37/72,51.5％）,差异具有统计学意义（P =0.022）.而瘤内间质CD163在2组间的表达无统计学意义（P =0.682）.IMPC中瘤内间质CD68的表达与病理学分期、组织学分级、淋巴结转移、脉管侵犯及Ki67的表达呈正相关（P＜0.05）,而与ER的表达呈负相关（P =0.037）.Kaplan-Meier单因素生存曲线分析显示,IMPC中瘤内间质CD68表达与无进展生存期（progression free survival,PFS）呈负相关（P =0.027）.结论 IMPC间质中CD68标记的TAMs可能在IMPC高侵袭、高转移的恶性生物学行为中发挥了重要的作用.     

Results of the national survey of borderline ovarian tumors in Spain

MATERIAL AND METHODS: Retrospective multi-center analysis of women diagnosed with borderline ovarian tumor and treated between January 1990 and December 1997. A national survey was conducted, in which 457 patients from 27 centers corresponding to ten of Spain's autonomous communities were analyzed. RESULTS: Four hundred fifty-seven women with borderline ovarian tumor were analyzed. The mean age of patients was 45.5+/-16.9 years. Of these, 390 patients (85.3%) were at stage I, 8 (1.8%) were at stage II and 36 (7.9%) at stage III. A bilateral tumor was observed in 63 women (13.8%). The mean tumor size was 14.2 cm and in 88 cases (19.3%) the tumor was on the surface of the ovary. Microinvasion was observed in 25 (5.5%) cases, and 29 women (6.3%) showed a micropapillary pattern. Study of the factors related to the appearance of peritoneal implants revealed positive tumor markers (OR 15.02: 1.9-32.9) and a tumor on the ovarian surface (OR 8.0: 1.8-127) to be independent risk factors. With respect to recurrence, the presence of peritoneal implants at the time of initial surgery (OR 3.4: 1.1-10.4) and signs of microinvasion in the anatomicopathological study (OR 5.5: 1.5-17.8) were found to be independent risk factors. The overall survival rate in our series was 97% with a mean follow-up of 88.3 months. The survival rate by stage was 97% for stage I, 100% for stage II and 97% for stage III. CONCLUSIONS: Although borderline ovarian tumors have an excellent prognosis, they are not exempt from a risk of recurrence. Characterization of patients with borderline ovarian tumor is essential in order to prevent their evolution. Likewise, the taking on board of risk factors will enable more selective treatments to be offered in each case.     

侵袭性结直肠微小乳头状癌25例

为探讨结直肠微小乳头状癌（MC）的临床病理及免疫组化特点，回顾分析1986年1月至2006年6月收治的285例结直肠癌患者中伴有MC成分的25例腺癌，以及45例普通型腺癌的病例资料，并进行对比分析。结果显示，MC与普通型腺癌多数为中等分化，MC的比例为5％～80％。MC和普通型腺癌相比，在淋巴血管浸润、淋巴结转移阳性率和最大平均数、远处转移以及肿瘤分期方面差异显著，P〈0．05。CK7、CK20、CDX2、MI．H1在MC及普通型结肠癌组织中表达差异无统计学意义，P〉0．05。结果表明，高分期的MC易发生淋巴管浸润、淋巴结转移及远处器官转移；MC在肿瘤中的比例与患者预后无关；MC的免疫构型与普通型腺癌无明显不同。     

含微乳头结构肺腺癌CT重建征象特征及上皮间质转化相关基因表达

目的 探讨含微乳头结构（MPP）肺腺癌具有的CT重建征象特征,上皮间质转化（EMT）相关分子表达情况以及它们之间的关系。 方法 选取含MPP侵袭性肺腺癌（IAC）37例、不含MPP 80例及其对应的癌旁组织,比较临床病理特征、CT重建征象;应用Real-time PCR及Western blotting检测EMT有关标识分子表达变化情况。 结果 含MPP组淋巴结转移比例较高、毛刺、胸膜凹陷征、实性及分叶比例较高（均P<0.001）。 含MPP组E-钙黏蛋白（cadherin）及β-连环蛋白（β-catenin）表达均下调（P<0.05）,N-cadherins、波形蛋白（vimentin）、Snail及转化生长因子（TGF）-β表达均上调（P<0.05）。有毛刺组E cadherin及β-catenin表达下调者所占比例较高,而vimentin表达上调者所占比例较高（均P<0.05）;实性结节组E-cadherin表达下调者所占比例较高,而N-cadherin及vimentin表达上调者所占比例较高（均P<0.05）。 结论 含MPP浸润性肺腺癌具有特征性CT重建征象,发生了EMT改变。其CT重建征象与EMT相关分子表达存在联系。     

Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients

Background

A new histological classification by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) for lung adenocarcinoma (LAC) was proposed recently, in which a micropapillary pattern (MPP) was described.

Objectives

This study aimed to evaluate the clinicopathological characteristics of LAC with MPP (LAC-MPP) and to investigate the correlation between LAC-MPP and epidermal growth factor receptor (EGFR) mutation status with the prognosis in Chinese patients.

Patients and methods

From May 2007 and February 2012, two hundred and forty-eight patients underwent resection and pathologically confirmed LAC. We classified all cases histologically according to the IASLC/ATS/ERS classification; an MPP ratio ≥5% was considered MPP-positive. Used Pearson's chi-square test to evaluate the relationships between EGFR mutation status and MPP status with patient clinicopathological characteristics.

Results

There were MPP-positive tumors (MPP ratio ≥5%) in 31.9% of cases (79/248); the MPP ratio correlated with TNM stage (p = 0.001) and lymph node metastasis (p = 0.03). EGFR mutation (EGFR-mut) was detected in 87 cases (34.3%); 161 cases had wild-type EGFR (EGFR-wt). EGFR mutation was present in 65% of the MPP-positive subtype. Patients with EGFR-mut tumors had significantly longer overall survival (OS) (p = 0.002). OS was also significantly longer in MPP-negative EGFR-mut or EGFR-wt patients (p < 0.001).

Conclusion

These findings indicate that EGFR-mut tumors are likelier to be MPP-positive subtypes and that MPP may be a novel potential pathological marker of poor prognosis in Chinese LAC patients.     

Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma

IntroductionHigh-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value.MethodsPatients who underwent lobectomy for pathologic stages II to III lung ADC with N1 or N2 LN metastases (N = 360; 2000–2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes.ResultsMIP and SOL in LN metastases were associated with a higher incidence of smoking history (p = 0.004), tumor necrosis (p = 0.013), and spread of tumor through air spaces (p < 0.0001), a higher prevalence of MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%–56%] versus 63% [48%–83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%–56%] versus 14% [4%–29%], p = 0.013), and higher CIR (5-y, 65% [50%–77%] versus 43% [25%–60%], p = 0.057). MIP and SOL in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR] = 1.81 [95% CI: 1.00–3.29], p = 0.05), LC-CID (HR = 3.10 [1.30–7.37], p = 0.01), and CIR (HR = 2.06 [1.09–3.90], p = 0.026).ConclusionsMIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC.     

术后放疗对局部晚期伴微乳头型肺腺癌的预后价值

目的 探讨术后放疗对局部晚期伴微乳头型肺腺癌(MPPAC)预后的影响。方法 回顾性分析天津医科大学肿瘤医院2012年1月至2014年12月根治性切除术后,经病理诊断为MPPAC的45例pN_2-3期患者临床资料。根据术后是否行放射治疗分为放疗组和未放疗组。比较两组患者的一般情况及总生存和无病生存情况。结果 全组患者的中位总生存期(overall survival,OS)为19.8个月,1年及2年总生存率分别为79.4%和30.3%。全组患者的中位无进展生存期(disease free survival, DFS)为13个月,1年及2年无进展生存率分别为59.3%和28.9%。放疗组和未放疗组患者的中位OS分别为22.3和13.4个月(χ²=13.329,P<0.05),中位DFS分别为16.2和10.4个月(χ²=7.972,P<0.05)。全组患者表皮生长因子受体(EGFR)基因突变率57.14%(20/35)。亚组分析发现,对于EGFR突变患者,放疗组和未放疗组中位OS分别为25.6和18.4个月(χ²=9.268,P<0.05),中位DFS分别为21.6和12.6个月(P>0.05);对于无EGFR突变的患者,放疗组和未放疗组中位OS分别为21.8和10.6个月(χ²=9.595,P<0.05),中位DFS分别为15.2和6.6个月(χ²=4.538,P<0.05)。结论 PORT能够改善根治术后pN_2-3期MPPAC患者生存,局部晚期根治术后的MPPAC患者仍需PORT。