Department of General Surgery, Visceral-, Thoracic-, Transplantation- and Pediatric-Surgery, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Arnold-Heller-Str. 3, Building C, 24105, Kiel, Germany.
Institute for Experimental Cancer Research, University of Kiel, Arnold-Heller-Str. 3, Building U30, 24105, Kiel, Germany.
J Cancer Res Clin Oncol. 2021 Nov;147(11):3313-3324. doi: 10.1007/s00432-021-03745-w. Epub 2021 Jul 24.
PURPOSE: HMGA2 has frequently been found in benign as well as malignant tumors and a significant association between HMGA2 overexpression and poor survival in different malignancies was described. In pancreatic ductal adenocarcinoma (PDAC), nuclear HMGA2 expression is associated with tumor dedifferentiation and presence of lymph node metastasis. Nevertheless, the impact of HMGA2 occurrence in other cell compartments is unknown. METHODS: Intracellular distribution of HMGA2 was analyzed in PDAC (n = 106) and peritumoral, non-malignant ducts (n = 28) by immunohistochemistry. Findings were correlated with clinico-pathological data. Additionally, intracellular HMGA2 presence was studied by Western blotting of cytoplasmic and nuclear fractions of cultured cells. RESULTS: HMGA2 was found in the cytoplasm and in the nucleus of cultured cells. In human tumor tissue, HMGA2 was also frequently found in the cytoplasm and the nucleus of tumor cells, however, nuclear staining was generally stronger. Direct comparison from tumor tissue with corresponding non-neoplastic peritumoral tissue revealed significantly stronger expression in tumors (p = 0.003). Of note, the nuclear staining was significantly stronger in lymph node metastatic cell nuclei compared to primary tumor cell nuclei (p = 0.049). Interestingly, cytoplasmic staining positively correlated with lymph vessel (p = 0.004) and venous invasion (p = 0.046). CONCLUSION: HMGA2 is a prognostic marker in PDAC. Firstly, we found a positive correlation for cytoplasmic HMGA2 expression with lympho-vascular invasion and, secondly, we found a significantly stronger nuclear expression of HMGA2 in cancer-positive lymph node nuclei compared to primary tumor cell nuclei. So far, the role of cytoplasmic HMGA2 is nearly unknown, however, our data lend support to the hypothesis that cytoplasmic HMGA2 expression is involved in nodal spread.
目的：HMGA2 频繁出现在良性和恶性肿瘤中，并且 HMGA2 过表达与不同恶性肿瘤的不良预后之间存在显著关联。在胰腺导管腺癌（PDAC）中，核 HMGA2 表达与肿瘤去分化和淋巴结转移有关。然而，HMGA2 在其他细胞区室中的存在的影响尚不清楚。
方法：通过免疫组织化学分析 PDAC（n=106）和肿瘤周围非恶性导管（n=28）中 HMGA2 的细胞内分布。研究结果与临床病理数据相关。此外，通过培养细胞的细胞质和核部分的 Western blot 研究细胞内 HMGA2 的存在。
结果：HMGA2 存在于培养细胞的细胞质和细胞核中。在人类肿瘤组织中，HMGA2 也经常存在于肿瘤细胞的细胞质和细胞核中，然而，核染色通常更强。直接比较肿瘤组织与相应的肿瘤周围非肿瘤组织显示，肿瘤中的表达明显更强（p=0.003）。值得注意的是，淋巴结转移细胞核中的核染色明显强于原发肿瘤细胞核中的核染色（p=0.049）。有趣的是，细胞质染色与淋巴管（p=0.004）和静脉侵犯（p=0.046）呈正相关。
结论：HMGA2 是 PDAC 的预后标志物。首先，我们发现细胞质 HMGA2 表达与淋血管侵犯呈正相关，其次，我们发现淋巴结阳性肿瘤细胞核中的 HMGA2 核表达明显强于原发肿瘤细胞核。到目前为止，细胞质 HMGA2 的作用几乎未知，然而，我们的数据支持细胞质 HMGA2 表达参与淋巴结播散的假说。
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