PCT has been drawing attention as a serum marker of serious bacterial infection such as sepsis. In the present study, we observed positive PCT expression in a half of the specimens of surgically resected LCNECs and carcinoids. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease course. In patients with SCLC, PCT was not detected in the tumor or serum. To the best of our knowledge, this is the first immunohistochemical study of the PCT expression in the lung tumor specimens.
There have been some reports of elevated serum PCT in patients with primary lung cancers [4, 6, 7]. Patout and colleagues retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia [4]. They showed that serum PCT was more elevated in those with neuroendocrine neoplasia and liver metastasis. Increased serum PCT was also associated with unfavorable prognosis [4]. Avrillon and colleagues evaluated 89 cases of newly diagnosed lung cancer with a pre-antineoplastic PCT assay and no signs of infection [6]. They found that serum PCT was positive in 42% of the cases and was strongly associated with the presence of a neuroendocrine component in histology. These findings indicated that serum PCT is occasionally elevated in patients with lung cancer, especially in those with neuroendocrine component and liver metastasis. In this study, none of the study subjects had liver metastasis, but both of 2 LCNEC patients with elevated serum PCT had remote metastases in brain and other organs. Although 5 patients with LCNEC and 2 with carcinoid had positive PCT expression in the tumor specimens, serum PCT levels were elevated only in 2 patients with LCNEC, both of whom showed high PCT expression. Taken together, at least in patients with LCNEC, elevated PCT levels in serum might be associated with high PCT expression in the tumor as well as remote metastasis.
In this study, we observed positive PCT expression in a half of the specimens of LCNEC and carcinoid, whereas none of the SCLC specimens showed PCT expression. Because all the SCLC specimens showed positive immunostaining of synaptophysin and NCAM, we considered that positive immunostaining of PCT in tissue specimens may be useful to exclude SCLC from other pulmonary NETs.
PCT is secreted from neuroendocrine cells in various organs, suggesting PCT production in NETs. In fact, immunohistochemical diagnosis of PCT-secreting NETs has been made in cases of medullary thyroid carcinoma [2] and pancreatic and gastrointestinal NETs [3, 8]. This is the first report confirming the expression of PCT in pulmonary neuroendocrine tumors.
PCT has a variety of biological effects. For example, PCT promotes the induction of nitric oxide synthase from sites of inflammation resulting in the onset of vasodilatation [9]. It also regulates cytokine reactions, inducing the onset of CD11b expression of monocytes and neutrophils [10]. These suggests that a PCT-producing cancer is progressive with poor prognosis. In fact, we observed that 2 patients with elevated PCT levels in serum had progressive disease with multiple metastasis.