Histone 1.5 (H1.5) Staining Directly Correlates with High Grade in Pulmonary Neuroendocrine Tumors
Huai-Bin M Ko, Jaclyn F Hechtman, Yayoi Kinoshita, David E Burstein, Mary B Beasley. Mount Sinai School of Medicine, New York
Background: Pulmonary neuroendocrine tumors (PNT) encompass a spectrum of tumors including the low and intermediate grade typical carcinoid (TC) and atypical carcinoid (AC) as well as the high grade large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). These tumors may pose diagnostic challenges on small biopsy specimens. Histone 1.5 (H1.5) is a member of the linker Histone 1 (H1) family. Levels of H1 are maximally phosphorylated in late G2 of the cell cycle, loosening the chromatin to allow transcription factors to bind. H1.5 has been shown to be the predominant H1 variant on active chromatin and chromatin poised for transcription. H1.5 has not been specifically evaluated in the spectrum of PNT. We evaluated Histone 1.5 staining in PNTs.
Design: 55 cases of PNT were retrieved, including carcinoid tumorlet (n=11), TC (n=17), AC (n=7), SCLC (n=16), and LCNEC (n=4). Immunohistochemical staining for H1.5 was performed (Abcam, 1:800). The staining was evaluated based on intensity (0 to 3+), and proportion of positive tumor cells (0-100%).
Results: H1.5 staining was universally found to be strictly nuclear, with no evidence of cytoplasmic staining in all 55 of the cases studied. Of 11 tumorlets, 1 showed nuclear immunoreactivity with 1+ intensity in 1% of the tumor cells; 2 showed weak/equivocal staining. Of 17 TC, 1 had nuclear immunoreactivity, intensity 2-3+, involving 15% of the tumor cells; 1 showed weak/equivocal staining involving 20% of cells. Of 7 AC, 2 cases had nuclear immunoreactivity, intensity 1-2+, involving 20% of cells; 3 showed weak/equivocal staining involving 5-20% of cells (average=12%). All 16 of the SCLC showed nuclear immunoreactivity, 1-3+ intensity, involving 30-100% of cells (average= 84%). All 4 of the LCNEC had nuclear immunoreactivity, intensity 1-3+, involving 40-100% of cells (average = 84%).
Conclusions: High nuclear expression of H1.5 in PNTs is directly correlated with high tumor grade. Low and intermediate grade TC and AC have a low incidence of positive staining for H1.5, with staining being weak and/or involving a small percentage of cells. In contrast, all high grade LCNEC and SCLC tumors showed positive staining for H1.5, with a high percentage of cells staining positive. These results are compatible with the theory that high expression of H1.5 reflects a constant state of DNA replication in high grade PNTs. In addition, staining for H1.5 may be useful in differentiating carcinoid tumors from high grade neuroendocrine tumors on small pulmonary biopsies.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 293, Tuesday Afternoon