Adrenomedullin expression does not correlate with survival in lung cancer

Abstract

It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin-embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2-4 (30-100%), which were significantly higher from the non-neo-plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo-plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies.

Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)

“…ADM is strongly induced by hypoxia, and overexpression of ADM has been reported in several malignant conditions, including pancreatic, colorectal, and renal cancer [ 30 , 34 , 35 , 36 , 37 ]. Plasma ADM has not previously been linked to disease progression in SCLC, and immunohistochemical studies found no or weak expression of ADM in SCLC tissue [ 38 , 39 ]. However, in line with our results, plasma ADM has been correlated with tumor progression in neuroendocrine carcinomas of various origin [ 40 ].…”

Massive digital gene expression analysis reveals different predictive profiles for immune checkpoint inhibitor therapy between adenocarcinoma and squamous cell carcinoma of advanced lung cancer

“…ADM regulates vascular tone and proliferation of fibroblasts and vascular smooth muscle cells [ 21 ]. Although there was no clinicopathological correlation, high ADM protein expression was observed in lung squamous cell carcinoma [ 22 ]. Increasing systemic levels of vasoactive peptides, including pro-ADM, are associated with improved tumor response in metastatic colorectal carcinoma patients treated with a bevacizumab-containing regimen [ 23 ].…”

Peptidergic Systems and Cancer: Focus on Tachykinin and Calcitonin/Calcitonin Gene-Related Peptide Families

“…However, AM expression did not correlate with the overall survival of patients, cancer stage, and tumor differentiation. The results reported by the authors do not support the role of AM as an independent survival agent for lung cancer [ 235 ]. The aryl hydrocarbon receptor is partially responsible for tobacco-induced carcinogenesis, and it has been reported that AM contributes to the carcinogenicity of tobacco-activated aryl hydrocarbon receptor products [ 236 ].…”

“…Lung cancer cells express CLR and RAMP2/3 [ 235 , 307 ]. AM appeared expressed in most non-small-cell and half of the small-cell lung carcinomas studied [ 308 ].…”