Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma

Samuel A. Henderson; Michael T. Tetzlaff; Penvadee Pattanaprichakul; Patricia Fox; Carlos A. Torres-Cabala; Roland L. Bassett; Victor G. Prieto; Hunter W. Richards; Jonathan L. Curry

doi:10.1111/cup.12383

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma

Samuel A. Henderson, Michael T. Tetzlaff, Penvadee Pattanaprichakul, Patricia Fox, Carlos A. Torres-Cabala, Roland L. Bassett, Victor G. Prieto, Hunter W. Richards, Jonathan L. Curry

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Background High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.

Methods Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.

Results H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035;HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.

Conclusions Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.

Original language	English (US)
Pages (from-to)	846-852
Number of pages	7
Journal	Journal of cutaneous pathology
Volume	41
Issue number	11
DOIs	https://doi.org/10.1111/cup.12383
State	Published - Nov 1 2014

Keywords

H3K79me3T80ph
Merkel cell carcinoma
PHH3
biomarker
histones

ASJC Scopus subject areas

Pathology and Forensic Medicine
Histology
Dermatology

MD Anderson CCSG core facilities

Biostatistics Resource Group

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10.1111/cup.12383

Cite this

Henderson, S. A., Tetzlaff, M. T., Pattanaprichakul, P., Fox, P., Torres-Cabala, C. A., Bassett, R. L., Prieto, V. G., Richards, H. W., & Curry, J. L. (2014). Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma. Journal of cutaneous pathology, 41(11), 846-852. https://doi.org/10.1111/cup.12383

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma. / Henderson, Samuel A.; Tetzlaff, Michael T.; Pattanaprichakul, Penvadee et al.
In: Journal of cutaneous pathology, Vol. 41, No. 11, 01.11.2014, p. 846-852.

Research output: Contribution to journal › Article › peer-review

Henderson, SA, Tetzlaff, MT, Pattanaprichakul, P, Fox, P, Torres-Cabala, CA , Bassett, RL , Prieto, VG, Richards, HW & Curry, JL 2014, 'Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma', Journal of cutaneous pathology, vol. 41, no. 11, pp. 846-852. https://doi.org/10.1111/cup.12383

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title = "Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma",

abstract = "Background High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.Methods Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.Results H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035;HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.Conclusions Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.",

keywords = "H3K79me3T80ph, Merkel cell carcinoma, PHH3, biomarker, histones",

author = "Henderson, {Samuel A.} and Tetzlaff, {Michael T.} and Penvadee Pattanaprichakul and Patricia Fox and Torres-Cabala, {Carlos A.} and Bassett, {Roland L.} and Prieto, {Victor G.} and Richards, {Hunter W.} and Curry, {Jonathan L.}",

note = "Publisher Copyright: {\textcopyright} 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2014",

month = nov,

day = "1",

doi = "10.1111/cup.12383",

language = "English (US)",

volume = "41",

pages = "846--852",

journal = "Journal of cutaneous pathology",

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T1 - Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma

AU - Henderson, Samuel A.

AU - Tetzlaff, Michael T.

AU - Pattanaprichakul, Penvadee

AU - Fox, Patricia

AU - Torres-Cabala, Carlos A.

AU - Bassett, Roland L.

AU - Prieto, Victor G.

AU - Richards, Hunter W.

AU - Curry, Jonathan L.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Background High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.Methods Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.Results H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035;HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.Conclusions Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.

AB - Background High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.Methods Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.Results H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035;HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.Conclusions Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.

KW - H3K79me3T80ph

KW - Merkel cell carcinoma

KW - PHH3

KW - biomarker

KW - histones

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SN - 0303-6987

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JO - Journal of cutaneous pathology

JF - Journal of cutaneous pathology

IS - 11

ER -

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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