PO.PR01.03 · 预防研究
缺氧诱导因子1-α在不同组织学类型子宫颈癌中的表达及其与肿瘤类型侵袭性的相关性：一项免疫组化研究
Expression of hypoxia-inducible factor 1-alpha in diverse histological types of uterine cervical carcinoma and correlation with the aggressiveness of tumor type: An immunohistochemical study
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摘要 Abstract
中文摘要
背景：
宫颈癌是全球女性癌症相关死亡的第四大原因，在南非发病率很高。高危型人乳头瘤病毒（HPV）以及遗传和表观遗传改变共同驱动宫颈癌变。缺氧诱导因子1-α（HIF-1alpha）在宫颈癌和其他实体瘤中频繁表达。在常氧条件下，HIF-1alpha经Von Hippel-Lindau通路降解，而缺氧则使其稳定，诱导血管生成因子。HIF-1alpha免疫组化已被提议作为预后和治疗标志物；然而，既往研究受限于队列较小、单中心设计和组织学变异。本研究评估了HIF-1alpha在宫颈癌各亚型中的表达及其与肿瘤侵袭性的关联。
方法：
我们对2017-2022年在比勒陀利亚大学（University of Pretoria）诊断的宫颈癌病例进行了一项回顾性研究。检索存档的甲醛固定石蜡包埋组织，共获得63例病例。进行HIF-1alpha免疫组化，三名病理学家采用改良的快速Allred系统独立评分染色，将综合评分超过零者归类为阳性。
结果：
HIF-1alpha表达在19/63例（30%）中为阳性，在44/63例（70%）中为阴性。基底样鳞状细胞癌占阳性病例的26%，CIN III样癌和乳头状鳞-尿路上皮癌各占21%，腺样基底细胞癌、乳头状鳞状细胞癌和透明细胞癌各占10%，腺鳞癌占5%。无腺样囊性癌、小细胞癌或绒毛腺管状癌为阳性。各亚型内的阳性率以乳头状鳞-尿路上皮癌（57%）和透明细胞癌（50%）最高，其次为基底样鳞状细胞癌（38%）、腺样基底细胞癌（33%）、CIN III样癌和乳头状鳞状细胞癌（28.5%）以及腺鳞癌（25%）。
结论：
HIF-1alpha在一部分宫颈癌中表达，主要见于与侵袭性行为相关的组织学变异，提示其与较差预后存在潜在联系。样本量有限和单中心设计需谨慎解读。仍需开展具有临床随访的更大规模多中心研究，以阐明HIF-1alpha能否指导宫颈癌的预后评估或靶向治疗。
查看英文原文 English abstract
Background:
Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide, with high prevalence in South Africa. High-risk human papillomavirus (HPV), along with genetic and epigenetic alterations, drives cervical carcinogenesis. Hypoxia-inducible factor 1-alpha (HIF-1alpha) is frequently expressed in cervical carcinoma and other solid tumors. Under normoxia, HIF-1alpha is degraded via the Von Hippel-Lindau pathway, while hypoxia stabilizes it, inducing angiogenic factors. HIF-1alpha immunohistochemistry has been proposed as a prognostic and therapeutic marker; however, previous studies are limited by small cohorts, single-center designs, and variable histology. This study assessed HIF-1alpha expression across cervical carcinoma subtypes and its association with tumor aggressiveness.
Methods:
We conducted a retrospective study of cervical carcinoma cases diagnosed at the University of Pretoria (2017-2022). Archived formalin-fixed paraffin-embedded tissues were retrieved, yielding 63 cases. HIF-1alpha immunohistochemistry was performed, and three pathologists independently scored staining using a modified quick Allred system, classifying cases as positive if the combined score exceeded zero.
Results:
HIF-1alpha expression was positive in 19/63 cases (30%) and negative in 44/63 (70%). Basaloid squamous cell carcinoma accounted for 26% of positive cases, CIN III-like and papillary squamous-urothelial carcinomas each 21%, adenoid basal, papillary squamous, and clear cell carcinomas 10% each, and adenosquamous carcinoma 5%. No adenoid cystic, small cell, or villoglandular carcinomas were positive. Positivity within subtypes was highest in papillary squamous-urothelial (57%) and clear cell (50%) carcinomas, followed by basaloid squamous cell (38%), adenoid basal (33%), CIN III-like and papillary squamous cell (28.5%), and adenosquamous (25%).
Conclusion:
HIF-1alpha is expressed in a subset of cervical carcinomas, predominantly in histological variants associated with aggressive behavior, suggesting a potential link with poorer prognosis. Limited sample size and single-center design warrant caution. Larger multicenter studies with clinical follow-up are needed to clarify whether HIF-1alpha can guide prognostic assessment or targeted therapy in cervical carcinoma.
利益披露 Disclosure
C. Ngobeni, None..
M. Bida, None..
B. Mosoane, None..
R. Marima, None..
T. Marutha, None..
Z. Dlamini, None..
T. Medupe, None.