Kimihiro Shimizu1, Yusuke Goto2, Reika Kawabata-Iwakawa3, Yoichi Ohtaki4, Seshiru Nakazawa4, Takehiko Yokobori5, Kai Obayashi4, Natsuko Kawatani4, Toshiki Yajima4, Kyoichi Kaira6, Akira Mogi4, Junko Hirato2, Masahiko Nishiyama3, Ken Shirabe4. 1. Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan. Electronic address: kmshimizu@gmail.com. 2. Department of Pathology, Gunma University Hospital, Gunma, Japan. 3. Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Gunma, Japan. 4. Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan. 5. Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan; Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Gunma, Japan. 6. Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Gunma, Japan.
Abstract
BACKGROUND: Stathmin-1 regulates microtubule dynamics and is associated with malignant phenotypes in non-small cell lung cancer (NSCLC). This study evaluated its diagnostic value for differentiating between NSCLC and high-grade lung neuroendocrine tumor (HGNET). METHODS: Stathmin-1 protein expression was assessed by immunohistochemistry in 414 NSCLC (305 adenocarcinoma [AD], 102 squamous cell carcinoma [SCC], 7 large-cell carcinoma), 5 typical carcinoid (low-grade lung neuroendocrine tumor), and 34 HGNET (17 small-cell carcinoma [SCLC] and 17 large-cell neuroendocrine carcinoma [LCNEC]) surgical specimens and 57 NSCLC (29 AD and 28 SCC) and 42 HGNET (17 LCNEC and 25 SCLC) biopsy specimens. We also analyzed stathmin-1 mRNA levels in 81 NSCLCs and 26 HGNETs with the use of reverse transcription-polymerase chain reaction. RESULTS: Among NSCLC samples, we saw high stathmin-1 protein expression in only three ADs, one SCC, and one large-cell carcinoma surgical samples, all five of which showed neuroendocrine characteristics in pathologic re-review; and low or intermediate expression in all five typical carcinoid surgical samples and all 57 NSCLC biopsy samples. In contrast, all HGNET surgical (n = 34) and biopsy (n = 42) samples showed high stathmin-1 expression. In reverse transcription-polymerase chain reaction, stathmin-1 expression was significantly higher in HGNET tissues than in NSCLC tissues (p < 0.001). CONCLUSIONS: Stathmin-1 expression can help in differentiating NSCLC from HGNET.
BACKGROUND:Stathmin-1 regulates microtubule dynamics and is associated with malignant phenotypes in non-small cell lung cancer (NSCLC). This study evaluated its diagnostic value for differentiating between NSCLC and high-grade lung neuroendocrine tumor (HGNET). METHODS:Stathmin-1 protein expression was assessed by immunohistochemistry in 414 NSCLC (305 adenocarcinoma [AD], 102 squamous cell carcinoma [SCC], 7 large-cell carcinoma), 5 typical carcinoid (low-grade lung neuroendocrine tumor), and 34 HGNET (17 small-cell carcinoma [SCLC] and 17 large-cell neuroendocrine carcinoma [LCNEC]) surgical specimens and 57 NSCLC (29 AD and 28 SCC) and 42 HGNET (17 LCNEC and 25 SCLC) biopsy specimens. We also analyzed stathmin-1 mRNA levels in 81 NSCLCs and 26 HGNETs with the use of reverse transcription-polymerase chain reaction. RESULTS: Among NSCLC samples, we saw high stathmin-1 protein expression in only three ADs, one SCC, and one large-cell carcinoma surgical samples, all five of which showed neuroendocrine characteristics in pathologic re-review; and low or intermediate expression in all five typical carcinoid surgical samples and all 57 NSCLC biopsy samples. In contrast, all HGNET surgical (n = 34) and biopsy (n = 42) samples showed high stathmin-1 expression. In reverse transcription-polymerase chain reaction, stathmin-1 expression was significantly higher in HGNET tissues than in NSCLC tissues (p < 0.001). CONCLUSIONS:Stathmin-1 expression can help in differentiating NSCLC from HGNET.