Comerci J T, Runowicz C D, Flanders K C, De Victoria C, Fields A L, Kadish A S, Goldberg G L
Department of Obstetrics and Gynecology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA.
Cancer. 1996 Mar 15;77(6):1107-14.
Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF-beta 1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-beta in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-beta 1.
Percent positive staining for the intracellular form of TGF-beta 1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas, (P = 0.002). Percent positive staining for the extracellular form of TGF-beta 1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007).
Decreased expression of intracellular TGF-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelia] cells may involve the loss of TGF-beta 1. Tumor progression may be indirectly promoted by TGF-beta 1 secreted into or produced by supporting stromal elements.
转化生长因子-β1（TGF-β1）是上皮细胞生长的强效抑制剂，但也能刺激基质细胞生长。对TGF-β1反应性的丧失或TGF-β1自身的丧失在宫颈上皮内瘤变（CIN）进展为浸润性宫颈癌过程中可能具有重要意义。方法：为检测子宫颈恶性转化早期阶段TGF-β的表达，采用免疫组化技术检查了11例宫颈上皮正常、15例CIN I-III、12例微浸润和18例浸润性鳞状细胞癌患者的石蜡包埋组织样本。用与细胞内和细胞外形式的TGF-β1反应的多克隆抗体对组织进行免疫染色。
TGF-β1细胞内形式的阳性染色百分比在正常上皮中为100%，在CIN中为73.3%，在浸润性癌中为44.1%（P = 0.002）。TGF-β1细胞外形式的阳性染色百分比在正常上皮下方的基质中为63.6%，在与CIN相关的基质中为60%，在浸润性癌周围的基质中为94.1%（P = 0.007）。
肿瘤上皮细胞中细胞内TGF-β1表达降低，而与浸润性宫颈癌相关的基质中细胞外TGF-β1表达增加，提示宫颈上皮细胞肿瘤转化的早期事件可能涉及TGF-β1的丧失。支持性基质成分分泌或产生的TGF-β1可能间接促进肿瘤进展。
