Alerraqi Ebtissam, Hasan Abdulkarim, Mandour Essam
New Giza University, Giza, Egypt.
Ministry of Health, Giza, Egypt.
Saudi Dent J. 2025 Jun 6;37(4-6):16. doi: 10.1007/s44445-025-00018-x.
Salivary gland mucoepidermoid carcinoma (MEC) is a morphologically challenging tumor, harboring a canonical CRTC1/3:MAML2 fusion, if investigated. However, the large cohorts available did not invesitgate the diagnosed cases adequately; leaving any mucin-producing malignancy possible MECs although >50% of salivary gland tumors secret mucin luminally or extra-luminally. This study examined the expression of stem cell markers Nanog, SOX2, OCT4, and MENA in salivary MEC using immunohistochemistry and to confer, whether or not, they may have a potential role in defining the tumoral molecular profile.
Forty well-investigated parotid MEC cases (p63+, p40+, CK7+, Ck5/6+, AE1/AE3+, EMA+, S100 -, ATF1 -, WT1-, SOX9 - and SOX10 -), all with MAML2 rearrangements and without EWSR1 alteration, were interrogated using immunohistochemical techniques to detect the immunoreactivity for Nanog, SOX2, OCT4, and MENA. Additionally, the POU5F1 FISH probe was used to confirm the immunohistochemical findings for OCT4.
Immunohistochemical analysis revealed negative or nonspecific immunoreactivity of NANOG, SOX2, and OCT4 antibodies throughout all examined specimens, inferring deficient pluripotency factor within MEC cellular oncogenesis. However, MENA was widely expressed in all cases. The results of the POU5 F1 FISH probe were consistent with the immunohistochemical data, showing no detectable expression of OCT4, Nanog or SOX2, across all 40 samples.
Cancer stem cells likely do not play any significant role in the pathogenesis of salivary MEC. The widespread expression of MENA, however, suggests that it has functions beyond promoting stemness or pluripotency in these tumors.
涎腺黏液表皮样癌(MEC)是一种形态学上具有挑战性的肿瘤,若进行检测,可发现其具有典型的CRTC1/3:MAML2融合基因。然而,现有的大型队列研究并未对诊断病例进行充分调查;尽管超过50%的涎腺肿瘤在管腔内或管腔外分泌黏液,但任何产生黏液的恶性肿瘤都有可能是MEC。本研究采用免疫组织化学方法检测涎腺MEC中干细胞标志物Nanog、SOX2、OCT4和MENA的表达,并探讨它们是否可能在定义肿瘤分子特征方面发挥潜在作用。
选取40例经过充分研究的腮腺MEC病例(p63+、p40+、CK7+、Ck5/6+、AE1/AE3+、EMA+、S100 -、ATF1 -、WT1-、SOX9 -和SOX10 -),所有病例均有MAML2重排且无EWSR1改变,采用免疫组织化学技术检测Nanog、SOX2、OCT4和MENA的免疫反应性。此外,使用POU5F1 FISH探针来确认OCT4的免疫组织化学结果。
免疫组织化学分析显示,在所有检测标本中,NANOG、SOX2和OCT4抗体呈阴性或非特异性免疫反应,提示MEC细胞发生肿瘤过程中多能性因子缺乏。然而,MENA在所有病例中均广泛表达。POU5 F1 FISH探针的结果与免疫组织化学数据一致,在所有40个样本中均未检测到OCT4、Nanog或SOX2的表达。
癌症干细胞可能在涎腺MEC的发病机制中不发挥任何重要作用。然而,MENA的广泛表达表明它在这些肿瘤中的功能不仅仅是促进干性或多能性。