Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil.
Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
Hum Pathol. 2014 May;45(5):917-25. doi: 10.1016/j.humpath.2014.01.015. Epub 2014 Jan 31.
Epidermal growth factor receptor (EGFR) protein expression was assessed by immunohistochemistry (IHC) in 150 cases of invasive vulvar squamous cell carcinoma. In addition, gene copy number status by fluorescence in situ hybridization was performed in a smaller set of samples. Results were correlated with patient's clinical data and prognostic factors. EGFR overexpression (2+ and 3+) was observed on the membrane in 24.66% and 21.33% of all cases, respectively. Higher EGFR expression was associated with depth of invasion (P = .0409) and disease recurrence (P = .0401). Cytoplasm staining was found in 21.33% of the cases and was associated with absence of nodal metastasis (P = .0061) and better survival (P = .0199). Intratumor heterogeneity of EGFR IHC staining was frequently observed (55.33%) and was associated with the presence of nodal metastasis (P = .0207) and tumor invasion (P = .0161). Worse survival outcomes have been demonstrated in tumors with EGFR heterogeneity (P = .0434). EGFR gene status evaluated by fluorescence in situ hybridization did not correlate with protein expression evaluated by IHC. In conclusion, EGFR cytoplasm staining has no link with poorer outcome; still, this pattern of staining is even more related to better prognosis. EGFR heterogeneity of staining correlated with more aggressive tumors, and presented to be an important marker of poor prognosis in vulvar squamous cell carcinoma. The usage of small biopsies or even tissue microarrays for vulvar cancer evaluation should be carefully reconsidered for the assessment of EGFR as the results may be misleading. Protein overexpression may be independent on gene amplification, showing that other molecular mechanisms than copy number variation may regulate protein expression of EGFR in vulvar cancer.
表皮生长因子受体 (EGFR) 蛋白表达通过免疫组织化学 (IHC) 在 150 例浸润性外阴鳞状细胞癌中进行评估。此外，还在较小的样本集中进行了荧光原位杂交的基因拷贝数状态检测。结果与患者的临床数据和预后因素相关。在所有病例中，分别有 24.66%和 21.33%的病例膜上出现 EGFR 过表达 (2+和 3+)。较高的 EGFR 表达与浸润深度 (P =.0409) 和疾病复发 (P =.0401) 相关。细胞质染色在 21.33%的病例中发现，与无淋巴结转移 (P =.0061) 和更好的生存 (P =.0199) 相关。EGFR IHC 染色的肿瘤内异质性经常观察到 (55.33%)，与淋巴结转移 (P =.0207) 和肿瘤侵袭 (P =.0161) 相关。在具有 EGFR 异质性的肿瘤中，已经证明了更差的生存结果 (P =.0434)。通过荧光原位杂交评估的 EGFR 基因状态与通过 IHC 评估的蛋白表达不相关。总之，EGFR 细胞质染色与较差的预后无关；然而，这种染色模式与更好的预后更相关。染色的 EGFR 异质性与侵袭性更强的肿瘤相关，并且被证明是外阴鳞状细胞癌不良预后的重要标志物。对于外阴癌评估，应仔细重新考虑使用小活检或甚至组织微阵列来评估 EGFR，因为结果可能会产生误导。蛋白过表达可能与基因扩增无关，表明除了拷贝数变异之外，其他分子机制可能调节外阴癌中 EGFR 的蛋白表达。
