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Abstract：
OBJECTIVE: Axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary (CUPAx) is a rare disease in women. This retrospective study intended to examine the clinicopathological features of CUPAx and compared CUPAx genetically with axillary lymph node metastases from breast cancer (BCAx), investigating differences in their biological behavior.
METHODS: We conducted the clinical and prognostic analysis of 58 CUPAx patients in West China Hospital spanning from 2009 to 2021. Gemonic profiling of 12 CUPAx patients and 16 BCAx patients was conducted by the FoundationOne CDx (F1CDx) platform. Moreover, we also compared the gene mutation spectrum and relevant pathways between the two groups and both TCGA and COSMIC databases.
RESULTS: The majority of the 58 CUPAx patients were HR-/HER2- subtype. Most patients received mastectomy combined radiotherapy (50 Gy/25f). CUPAx patients who received mastectomy instead of breast-conserving surgery had a more favorable overall prognosis. Radiotherapy in chest wall/breast and supraclavicular/infraclavicular fossa was the independent prognostic factor (HR = 0.05, 95%CI = 0.00-0.93, P = 0.04). In 28 sequencing samples (CUPAx, n = 12, BCAx, n = 16) and 401 TCGA-BRCA patients, IRS2 only mutated in CUPAx (33.33%) but amplified in BCAx (11.11%) and TCGA-BRCA (1.5%). Pathway analysis revealed that BCAx had more NOTCH pathway mutations than CUPAx. Enrichment analysis showed that CUPAx enriched more in mammary development and PML bodies than BCAx, but less in the positive regulation of kinase activity.
CONCLUSIONS: More active treatment methods, like chemotherapy, mastectomy and postoperative radiotherapy, could improve the prognosis of CUPAx. The differential mutation genes of CUPAx and BCAx might be associated with their respective biological behaviors like invasiveness and prognosis.
METHODS: We conducted the clinical and prognostic analysis of 58 CUPAx patients in West China Hospital spanning from 2009 to 2021. Gemonic profiling of 12 CUPAx patients and 16 BCAx patients was conducted by the FoundationOne CDx (F1CDx) platform. Moreover, we also compared the gene mutation spectrum and relevant pathways between the two groups and both TCGA and COSMIC databases.
RESULTS: The majority of the 58 CUPAx patients were HR-/HER2- subtype. Most patients received mastectomy combined radiotherapy (50 Gy/25f). CUPAx patients who received mastectomy instead of breast-conserving surgery had a more favorable overall prognosis. Radiotherapy in chest wall/breast and supraclavicular/infraclavicular fossa was the independent prognostic factor (HR = 0.05, 95%CI = 0.00-0.93, P = 0.04). In 28 sequencing samples (CUPAx, n = 12, BCAx, n = 16) and 401 TCGA-BRCA patients, IRS2 only mutated in CUPAx (33.33%) but amplified in BCAx (11.11%) and TCGA-BRCA (1.5%). Pathway analysis revealed that BCAx had more NOTCH pathway mutations than CUPAx. Enrichment analysis showed that CUPAx enriched more in mammary development and PML bodies than BCAx, but less in the positive regulation of kinase activity.
CONCLUSIONS: More active treatment methods, like chemotherapy, mastectomy and postoperative radiotherapy, could improve the prognosis of CUPAx. The differential mutation genes of CUPAx and BCAx might be associated with their respective biological behaviors like invasiveness and prognosis.
摘要：
目的：腺癌或原发灶不明的低分化癌（CUPAx）的腋窝淋巴结转移是女性的罕见疾病。这项回顾性研究旨在检查CUPAx的临床病理特征，并将CUPAx与乳腺癌（BCAx）的腋窝淋巴结转移进行遗传比较。调查它们生物学行为的差异。
方法：对华西医院2009-2021年收治的58例CUPAx患者进行临床及预后分析。通过FoundationOneCDx(F1CDx)平台对12例CUPAx患者和16例BCAx患者进行了Gemonic分析。此外，我们还比较了两组之间的基因突变谱和相关通路以及TCGA和COSMIC数据库.
结果：58例CUPAx患者中大多数为HR-/HER2-亚型。大多数患者接受乳房切除术联合放疗（50Gy/25f）。接受乳房切除术而不是保乳手术的CUPAx患者具有更良好的总体预后。胸壁/乳腺、锁骨上/锁骨下窝放疗是影响预后的独立因素(HR=0.05,95CI=0.00～0.93,P=0.04)。在28个测序样本中（CUPAx，n=12,BCAx,n=16）和401名TCGA-BRCA患者，IRS2仅在CUPAx(33.33%)中突变,但在BCAx(11.11%)和TCGA-BRCA(1.5%)中扩增。通路分析显示BCAx比CUPAx有更多的NOTCH通路突变。富集分析表明，CUPAx在乳腺发育和PML体中的富集程度高于BCAx，但对激酶活性的正向调节较少。
结论：更积极的治疗方法，比如化疗，乳房切除术和术后放疗，可以改善CUPAx的预后。CUPAx和BCAx的差异突变基因可能与它们各自的生物学行为如侵袭性和预后有关。
方法：对华西医院2009-2021年收治的58例CUPAx患者进行临床及预后分析。通过FoundationOneCDx(F1CDx)平台对12例CUPAx患者和16例BCAx患者进行了Gemonic分析。此外，我们还比较了两组之间的基因突变谱和相关通路以及TCGA和COSMIC数据库.
结果：58例CUPAx患者中大多数为HR-/HER2-亚型。大多数患者接受乳房切除术联合放疗（50Gy/25f）。接受乳房切除术而不是保乳手术的CUPAx患者具有更良好的总体预后。胸壁/乳腺、锁骨上/锁骨下窝放疗是影响预后的独立因素(HR=0.05,95CI=0.00～0.93,P=0.04)。在28个测序样本中（CUPAx，n=12,BCAx,n=16）和401名TCGA-BRCA患者，IRS2仅在CUPAx(33.33%)中突变,但在BCAx(11.11%)和TCGA-BRCA(1.5%)中扩增。通路分析显示BCAx比CUPAx有更多的NOTCH通路突变。富集分析表明，CUPAx在乳腺发育和PML体中的富集程度高于BCAx，但对激酶活性的正向调节较少。
结论：更积极的治疗方法，比如化疗，乳房切除术和术后放疗，可以改善CUPAx的预后。CUPAx和BCAx的差异突变基因可能与它们各自的生物学行为如侵袭性和预后有关。
