Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania
Department of Pathology, University of Oradea, Oradea, Romania.
Int J Gynecol Cancer. 2021 Feb;31(2):177-184. doi: 10.1136/ijgc-2020-001893. Epub 2020 Nov 11.
Prognostic factors for endocervical adernocarcinomas are well known, but little is known about prognostic biomarkers influencing outcome for the newly defined International Federation of Gynecology and Obstetrics (FIGO) 2018 IB sub-stages. The aim of this study was to identify prognostic biomarkers influencing recurrence-free and overall survival for FIGO 2018 stage IB cervical adenocarcinoma sub-types. We sought to identify these factors using a large international multi-institutional series of cases.
Stage IB endocervical adenocarcinomas were retrospectively collected from nine international institutions; full slide sets (n=464) were used to assign prognostic biomarkers. Inclusion criteria were the following: FIGO stage IB endocervical adenocarcinomas with follow-up in which all paraffin blocks/glass slides were available for review and/or additional studies and the patient was surgically treated from 1985 to 2019. The types of specimens included in the study were conizations, trachelectomies, and simple/radical hysterectomies with or without lymph node samples. We excluded in situ carcinomas, squamous cell carcinomas, adenosquamous carcinomas, tumors with a neuroendocrine component, carcinosarcomas, and any tumor showing clinical, macroscopic, or microscopic features suggesting a lower uterine segment, uterine corpus, or an adnexal primary origin. Tumors treated with neoadjuvant chemotherapy and/or radiation therapy were also excluded, as well as biopsies and loop electrosurgical excision procedures.
Of 464 cases, 225 (48%) were stage IB1, 177 (38%) were stage IB2, and 62 (13%) were stage IB3. Five-year and 10-year recurrence-free survivals were statistically different among stage IB sub-types (p=0.005). Silva pattern of invasion was significant for recurrence-free survival at 5 and 10 years (p=0.04); overall survival and recurrence-free survival were higher in human papillomavirus (HPV)-associated cases (p=0.007 and p=0.001, respectively) and in cases without lymphovascular invasion (p=0.004 and p=0.00001, respectively). Factors that significantly influenced recurrence-free survival were HPV-independent status (p=0.05; HR 2.31; 95% CI 1.02 to 5.46), presence of lymphovascular invasion (p=0.011; HR 3.50; 95% CI 1.33 to 9.19), and presence of lymph node metastasis (p=0.016; HR 2.66; 95% CI 1.20 to 5.90).
HPV status and the presence of lymphovascular invasion are prognosticators in stage IB endocervical adenocarcinoma sub-types. These parameters should be included in future sub-staging modifications of FIGO stage IB endocervical adenocarcinomas and in treatment strategies.
宫颈内膜腺癌的预后因素已得到充分研究，但对于新定义的国际妇产科联合会（FIGO）2018 年 IB 亚分期中影响结局的预后生物标志物知之甚少。本研究旨在确定影响 FIGO 2018 年 IB 期宫颈内膜腺癌亚型无复发生存和总生存的预后生物标志物。我们试图使用大型国际多机构系列病例来识别这些因素。
从 9 个国际机构回顾性收集 IB 期宫颈内膜腺癌病例；使用完整切片集（n=464）来分配预后生物标志物。纳入标准如下：FIGO 分期 IB 期宫颈内膜腺癌，有随访，所有石蜡块/载玻片均可用于复查和/或进一步研究，且患者于 1985 年至 2019 年接受手术治疗。研究中包含的标本类型有子宫颈锥切术、子宫颈切除术和单纯/根治性子宫切除术，伴或不伴淋巴结样本。我们排除了原位癌、鳞状细胞癌、腺鳞癌、具有神经内分泌成分的肿瘤、癌肉瘤以及任何具有临床、大体或镜下特征提示起源于子宫下段、子宫体或附件的肿瘤。也排除了接受新辅助化疗和/或放疗的肿瘤，以及活检和环形电切术。
464 例病例中，225 例（48%）为 IB1 期，177 例（38%）为 IB2 期，62 例（13%）为 IB3 期。IB 亚型之间 5 年和 10 年无复发生存率存在统计学差异（p=0.005）。侵袭的 Silva 模式在 5 年和 10 年时对无复发生存率有显著影响（p=0.04）；HPV 相关病例的总生存率和无复发生存率更高（p=0.007 和 p=0.001），无淋巴血管侵犯病例的总生存率和无复发生存率更高（p=0.004 和 p=0.00001）。显著影响无复发生存率的因素包括 HPV 独立状态（p=0.05；HR 2.31；95%CI 1.02 至 5.46）、存在淋巴血管侵犯（p=0.011；HR 3.50；95%CI 1.33 至 9.19）和存在淋巴结转移（p=0.016；HR 2.66；95%CI 1.20 至 5.90）。
HPV 状态和淋巴血管侵犯的存在是 IB 期宫颈内膜腺癌亚型的预后因素。这些参数应纳入 FIGO 分期 IB 期宫颈内膜腺癌的亚分期修改和治疗策略中。
