Chitguppi Chandala, Rabinowitz Mindy R, Johnson Jennifer, Bar-Ad Voichita, Fastenberg Judd H, Molligan Jeremy, Berman Ethan, Nyquist Gurston G, Rosen Marc R, Evans James E, Mardekian Stacey K
Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States.
Department of Hematology and Medical Oncology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States.
J Neurol Surg B Skull Base. 2020 Dec;81(6):610-619. doi: 10.1055/s-0039-1693659. Epub 2019 Jul 24.
Due to the diverse histopathologic features and variable survival rates seen in sinonasal undifferentiated carcinoma (SNUC), it is likely that this diagnostic entity is comprised of a heterogonous group of morphologically undifferentiated tumors. As advancements in molecular testing have led to a better understanding of tumor biology, it has become increasingly evident that SNUC may actually encompass several tumor subtypes with different clinical behavior. As a result, it is also likely that all SNUC patients cannot be treated in the same fashion. Recent investigations have identified loss of the tumor suppressor (INI1) expression in a subset of undifferentiated sinonasal tumors and extrasinonasal tumors and, studies have suggested that this genetic aberration may be a poor prognostic marker. The objective of this study was to identify differential expression of in SNUC and to analyze and compare the survival outcomes in SNUC patients with and without expression. All cases of undifferentiated or poorly differentiated neoplasms of the sinonasal tract treated between 2007 and 2018 at a single tertiary care institution were selected. All cases of SNUC were tested for status by immunohistochemistry (IHC). Clinical parameters were analyzed using Student's -test and Fischer's test. Kaplan-Meier methods were used to estimate survival durations, while comparison between both the subgroups was done using the log-rank test. Statistical analysis was performed with the use of SPSS software, Version 25 (IBM, New York, NY, United States). Fourteen cases of SNUC were identified. Approximately two-thirds (64%; = 9) of patients were male and the majority (79%; = 11) were between fifth to seventh decade. Skull base and orbital invasion were seen in 79% ( = 11) and 93% ( = 13) of cases, respectively. Fifty-seven percent of tumors ( = 8) retained expression by IHC (SR-SNUC), while the remaining 43% ( = 6) showed loss of expression and, thus, were considered as -deficient (SD-SNUC). Although clinicopathological features and treatment modalities were similar, SD-SNUC showed poorer (OS: = 0.07; disease free survival [DFS]: = 0.02) overall survival (OS) and DFS on Kaplan-Meier curves. Additionally, SD-SNUC showed higher recurrence (75 vs. 17%) and mortality (67 vs. 14%) (hazard rate = 8.562; = 0.05) rates. Both OS (28.82 ± 31.15 vs. 53.24 ± 37.50) and DFS durations (10.62 ± 10.26 vs. 43.79 ± 40.97) were consistently worse for SD-SNUC. Five-year survival probabilities were lower for SD-SNUC (0.33 vs. 0.85). SNUC represents a heterogeneous group of undifferentiated sinonasal malignancies. Based on the status of expression, the two subgroups SD-SNUC and SR-SNUC appear to represent distinct clinical entities, with loss of expression conferring an overall worse prognosis.
由于鼻窦未分化癌(SNUC)具有多样的组织病理学特征和不同的生存率,这个诊断实体可能是由一组形态学上未分化的异质性肿瘤组成。随着分子检测技术的进步使人们对肿瘤生物学有了更好的理解,越来越明显的是,SNUC实际上可能包含几种具有不同临床行为的肿瘤亚型。因此,所有SNUC患者也不太可能采用相同的治疗方式。最近的研究已经在一部分未分化鼻窦肿瘤和鼻窦外肿瘤中发现了肿瘤抑制因子(INI1)表达缺失,并且研究表明这种基因畸变可能是一个不良预后标志物。本研究的目的是确定SNUC中INI1的差异表达,并分析和比较有或无INI1表达的SNUC患者的生存结果。
选取了2007年至2018年在一家三级医疗机构接受治疗的所有鼻窦未分化或低分化肿瘤病例。所有SNUC病例均通过免疫组织化学(IHC)检测INI1状态。使用学生t检验和费舍尔检验分析临床参数。采用Kaplan-Meier方法估计生存时间,而两个亚组之间的比较则使用对数秩检验。使用SPSS软件25版(美国纽约州IBM公司)进行统计分析。
共确定了14例SNUC病例。约三分之二(64%;n = 9)的患者为男性,大多数(79%;n = 11)年龄在五至七旬。分别有79%(n = 11)和93%(n = 13)的病例出现颅底和眼眶侵犯。57%的肿瘤(n = 8)通过IHC检测保留INI1表达(SR-SNUC),而其余43%(n = 6)显示INI1表达缺失,因此被视为INI1缺陷型(SD-SNUC)。尽管临床病理特征和治疗方式相似,但在Kaplan-Meier曲线上,SD-SNUC的总生存期(OS:p = 0.07;无病生存期[DFS]:p = 0.02)和DFS表现较差。此外,SD-SNUC的复发率(75%对17%)和死亡率(67%对14%)(风险率 = 8.562;p = 0.05)更高。SD-SNUC的OS(28.82±31.15对53.24±37.50)和DFS持续时间(10.62±10.26对43.79±40.97)始终更差。SD-SNUC的五年生存概率更低(0.33对0.85)。
SNUC代表了一组异质性的未分化鼻窦恶性肿瘤。基于INI1表达状态,两个亚组SD-SNUC和SR-SNUC似乎代表了不同的临床实体,INI