Kocheri Nadeem, Chatterjee Priti, Agarwal Shipra, Sharma Mehar C, Ballal Sanjana, Bal Chandrasekhar, Chumber Sunil
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Pathology, Lady Hardinge Medical, College, New Delhi, India.
Indian J Endocrinol Metab. 2024 Nov-Dec;28(6):617-621. doi: 10.4103/ijem.ijem_235_23. Epub 2024 Dec 30.
Papillary thyroid carcinoma (PTC) has an excellent prognosis, but few cases are treatment-resistant. To check the applicability of combined and MEK-targeted therapy, the current study correlated with the MAPK pathway activation status in a cohort of PTCs. The prognostic relevance of and the usability of immunohistochemistry (IHC) for detecting the mutation were also assessed.
Randomly selected 50 PTC and 15 non-PTC cases were re-classified according to the 2022 WHO classification. The mutation status was compared with the IHC of BRAF, pERK1/2, pMEK1/2, and clinicopathological variables, including response to radioactive iodine and disease-free survival.
mutation was present in 38%. Most (87.8%) cases were immunopositive for pMEK1/2 and 40% for pMEK1/2. Although mutation did not correlate with the MAPK activation status, it had an adverse impact on tumour sensitivity to radioiodine ( < 0.05). Five of the seven radioiodine-resistant tumours were -mutated. An Allred cut-off score of 7 had a sensitivity of 100% and a specificity of 84% for detecting the mutation by IHC. All the non-PTC cases were -wild type, but 20% showed weak immunopositivity for mutated protein and were scored 6.
-mutated PTCs are more likely to be RAI-resistant. MAPK pathway activation status did not vary significantly with mutation. Immunopositivity for pMEK1/2 in most suggests a scope for MEK1-targeted therapy in recalcitrant PTC cases even in the absence of the mutation. In addition, IHC is a reliable technique for detecting mutation but needs validation by correlation with molecular studies.
甲状腺乳头状癌（PTC）预后良好，但少数病例对治疗耐药。为检验联合及MEK靶向治疗的适用性，本研究在一组PTC病例中关联了[具体基因]与MAPK通路激活状态。还评估了[具体基因]的预后相关性及免疫组化（IHC）检测该突变的可用性。
根据2022年世界卫生组织分类对随机选取的50例PTC和15例非PTC病例重新分类。将[具体基因]突变状态与BRAF、pERK1/2、pMEK1/2的免疫组化及临床病理变量进行比较，包括对放射性碘的反应和无病生存期。
38%存在[具体基因]突变。大多数（87.8%）病例pMEK1/2免疫阳性，40%病例pMEK1/2免疫阳性。虽然[具体基因]突变与MAPK激活状态无关，但对肿瘤对放射性碘的敏感性有不利影响（P<0.05）。7例放射性碘抵抗肿瘤中有5例为[具体基因]突变。Allred截断分数为7时，通过IHC检测[具体基因]突变的敏感性为100%，特异性为84%。所有非PTC病例均为[具体基因]野生型，但20%病例对突变蛋白呈弱阳性免疫反应，评分为6分。
[具体基因]突变的PTC更可能对放射性碘抵抗。MAPK通路激活状态随[具体基因]突变无显著变化。大多数病例中pMEK1/2免疫阳性表明，即使在无[具体基因]突变的情况下，对于难治性PTC病例，MEK1靶向治疗也有应用空间。此外，IHC是检测[具体基因]突变的可靠技术，但需要通过与分子研究的相关性进行验证。
