Skip to main content
Erschienen in: Discover Oncology 4/2018

18.06.2018 | Original Paper

Androgen Receptor and Ki67 Expression and Survival Outcomes in Non-small Cell Lung Cancer

verfasst von: Laurel Grant, Shantanu Banerji, Leigh Murphy, David E. Dawe, Craig Harlos, Yvonne Myal, Zoann Nugent, Anne Blanchard, Carla R. Penner, Gefei Qing, Marshall W. Pitz

Erschienen in: Discover Oncology | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome. Using the MTB, we performed immunohistochemistry on lung cancer tissue to determine expression of the AR and Ki67. These were then correlated with patient outcome. Of the 136 cases, 55% were female and 55% were adenocarcinoma. AR expression was not independently associated with outcome. Ki67 was associated with a significantly higher hazard ratio for death and recurrence (HR 2.19, 95% CI 1.30–3.70; HR 1.92, 95% CI 1.07–3.46, respectively). AR expression modified the effect of Ki67 on outcome, such that when both were expressed, there was no association with recurrence or survival (HR 2.39, 95% CI 1.31–4.36 for AR− Ki67+ vs HR 1.54, 95% CI 0.44–5.37 for AR+ Ki67+). Ki67 was associated with poorer outcomes alone. AR status alone was not associated with outcome. Although the mechanism remains unclear, AR status seems to negate the association of a high Ki67 and poor outcome.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Pitz MW, Musto G, Demers AA, Kliewer EV (2009) Survival and treatment pattern of non-small cell lung cancer over 20 years. J Thorac Oncol 4(3):492–498CrossRefPubMed Pitz MW, Musto G, Demers AA, Kliewer EV (2009) Survival and treatment pattern of non-small cell lung cancer over 20 years. J Thorac Oncol 4(3):492–498CrossRefPubMed
3.
Zurück zum Zitat Ridge CA, Mcerlean AM, Ginsberg AM (2013) Epidemiology of lung cancer. Semin Interv Radiol 30(2):93–98CrossRef Ridge CA, Mcerlean AM, Ginsberg AM (2013) Epidemiology of lung cancer. Semin Interv Radiol 30(2):93–98CrossRef
4.
Zurück zum Zitat Dawe DE, Pond GR, Ellis PM (2016) Assessment of referral and chemotherapy treatment patterns for elderly patients with non small-cell lung cancer. Clin Lung Cancer 17(6):563–572CrossRefPubMed Dawe DE, Pond GR, Ellis PM (2016) Assessment of referral and chemotherapy treatment patterns for elderly patients with non small-cell lung cancer. Clin Lung Cancer 17(6):563–572CrossRefPubMed
5.
Zurück zum Zitat Bach PB, Kris MG (2016) Lung cancer in US women: a contemporary epidemic. JAMA 291(14):1763–1768 Bach PB, Kris MG (2016) Lung cancer in US women: a contemporary epidemic. JAMA 291(14):1763–1768
6.
Zurück zum Zitat Thomas L, Doyle LA, Edelman MJ (2005) Lung cancer in women: emerging differences in epidemiology, biology, and therapy. Chest 128:370–381CrossRefPubMed Thomas L, Doyle LA, Edelman MJ (2005) Lung cancer in women: emerging differences in epidemiology, biology, and therapy. Chest 128:370–381CrossRefPubMed
7.
Zurück zum Zitat Pitz MW, Musto G, Navaratnam S (2013) Sex as an independent prognostic factor in a population-based, non-small cell lung cancer cohort. Can Respir J 20(1):30–35CrossRefPubMedPubMedCentral Pitz MW, Musto G, Navaratnam S (2013) Sex as an independent prognostic factor in a population-based, non-small cell lung cancer cohort. Can Respir J 20(1):30–35CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Mikkonen L, Pihlajamaa P, Sahu B, Zhang F, Jänne OA (2010) Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol 314:14–24CrossRef Mikkonen L, Pihlajamaa P, Sahu B, Zhang F, Jänne OA (2010) Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol 314:14–24CrossRef
9.
Zurück zum Zitat Recchia AG, Musti AM, Lanzino M, Panno ML, Turano E, Zumpano R, Belfiore A, Andò S, Maggiolini M (2009) A cross-talk between the androgen receptor and the epidermal growth factor receptor leads to p38MAPK-dependent activation of mTOR and cyclinD1 expression in prostate and lung cancer cells. Int J Biochem Cell Biol 41:603–614CrossRefPubMed Recchia AG, Musti AM, Lanzino M, Panno ML, Turano E, Zumpano R, Belfiore A, Andò S, Maggiolini M (2009) A cross-talk between the androgen receptor and the epidermal growth factor receptor leads to p38MAPK-dependent activation of mTOR and cyclinD1 expression in prostate and lung cancer cells. Int J Biochem Cell Biol 41:603–614CrossRefPubMed
10.
Zurück zum Zitat Beattie CW, Hansen NW, Thomas PA (1985) Steroid receptors in human lung cancer. Cancer Res 45:4206–4214PubMed Beattie CW, Hansen NW, Thomas PA (1985) Steroid receptors in human lung cancer. Cancer Res 45:4206–4214PubMed
11.
Zurück zum Zitat De Azambuja E, Cardoso F, de Castro G Jr, Colozza M, Durbecq V, Sotiriou C, Larsimont D, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients. Br J Cancer 96:1504–1513CrossRefPubMedPubMedCentral De Azambuja E, Cardoso F, de Castro G Jr, Colozza M, Durbecq V, Sotiriou C, Larsimont D, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients. Br J Cancer 96:1504–1513CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Klapper W, Hoster E, Determann O, Cabeçadas J, Campo E, Cogliatti S, Kodet R, Krivolapov YA, Loddenkemper C, Stein H, Müller-hermelink K, Rosenwald A (2009) Ki-67 as a prognostic marker in mantle cell lymphoma—consensus guidelines of the pathology panel of the European MCL Network. J Hematopathol 2:103–111CrossRef Klapper W, Hoster E, Determann O, Cabeçadas J, Campo E, Cogliatti S, Kodet R, Krivolapov YA, Loddenkemper C, Stein H, Müller-hermelink K, Rosenwald A (2009) Ki-67 as a prognostic marker in mantle cell lymphoma—consensus guidelines of the pathology panel of the European MCL Network. J Hematopathol 2:103–111CrossRef
13.
Zurück zum Zitat Warth A, Cortis J, Soltermann A, Meister M, Budczies J, Stenzinger A, Goeppert B, Thomas M (2014) Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer 111:1222–1229CrossRefPubMedPubMedCentral Warth A, Cortis J, Soltermann A, Meister M, Budczies J, Stenzinger A, Goeppert B, Thomas M (2014) Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer 111:1222–1229CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Martin B, Paesmans M, Mascaux C, Berghmans T, Lothaire P, Meert A, Lafitte J, Sculier J (2004) Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91:2018–2025CrossRefPubMedPubMedCentral Martin B, Paesmans M, Mascaux C, Berghmans T, Lothaire P, Meert A, Lafitte J, Sculier J (2004) Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91:2018–2025CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Tabata K, Tanaka T, Hayashi T, Hori T, Nunomura S (2014) Ki-67 is a strong prognostic marker of non-small cell lung cancer when tissue heterogeneity is considered. BMC Clin Pathol 14(23):1–8 Tabata K, Tanaka T, Hayashi T, Hori T, Nunomura S (2014) Ki-67 is a strong prognostic marker of non-small cell lung cancer when tissue heterogeneity is considered. BMC Clin Pathol 14(23):1–8
17.
Zurück zum Zitat Skliris GP, Leygue E, Watson PH, Murphy LC (2006) Expression of oestrogen receptor-b in oestrogen receptor-a negative human breast tumours. Br J Cancer 95:616–626CrossRefPubMedPubMedCentral Skliris GP, Leygue E, Watson PH, Murphy LC (2006) Expression of oestrogen receptor-b in oestrogen receptor-a negative human breast tumours. Br J Cancer 95:616–626CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Skliris GP, Rowan BG, Al-dhaheri M, Williams C, Troup S (2012) Immunohistochemical validation of multiple phospho-specific epitopes for estrogen receptor α (ERα) in tissue microarrays of ERα positive human breast carcinomas. Breast Cancer Res Treat 118:443–453CrossRef Skliris GP, Rowan BG, Al-dhaheri M, Williams C, Troup S (2012) Immunohistochemical validation of multiple phospho-specific epitopes for estrogen receptor α (ERα) in tissue microarrays of ERα positive human breast carcinomas. Breast Cancer Res Treat 118:443–453CrossRef
19.
Zurück zum Zitat Navaratnam S, Skliris G, Qing G, Shepherd FA, Nowatzki J, Demers A (2012) Differential role of estrogen receptor beta in early versus metastatic non-small cell lung cancer. Horm Cancer 3:93–100CrossRefPubMed Navaratnam S, Skliris G, Qing G, Shepherd FA, Nowatzki J, Demers A (2012) Differential role of estrogen receptor beta in early versus metastatic non-small cell lung cancer. Horm Cancer 3:93–100CrossRefPubMed
20.
Zurück zum Zitat Berardi R, Morgese F, Santinelli A, Onofri A, Biscotti A, Brunelli A, Caramanti M, Savini A, De Lisa M, Ballatore Z, Pompili C, Salati M, Torniai M, Cascinu S (2016) Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex. Oncotarget 7:82648–82657PubMedPubMedCentral Berardi R, Morgese F, Santinelli A, Onofri A, Biscotti A, Brunelli A, Caramanti M, Savini A, De Lisa M, Ballatore Z, Pompili C, Salati M, Torniai M, Cascinu S (2016) Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex. Oncotarget 7:82648–82657PubMedPubMedCentral
21.
Zurück zum Zitat Maynard PV, Davies CJ, Blamey RW, Elston CW, Johnson J, Griffiths K (1978) Relationship between oestrogen-receptor content and histologic grade in human primary breast tumors. Br J Cancer 38:745–748CrossRefPubMedPubMedCentral Maynard PV, Davies CJ, Blamey RW, Elston CW, Johnson J, Griffiths K (1978) Relationship between oestrogen-receptor content and histologic grade in human primary breast tumors. Br J Cancer 38:745–748CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Harlos C, Musto G, Lambert P, Ahmed R, Pitz MW (2015) Androgen pathway manipulation and survival in patients with lung cancer. Horm Cancer 6:120–127CrossRefPubMed Harlos C, Musto G, Lambert P, Ahmed R, Pitz MW (2015) Androgen pathway manipulation and survival in patients with lung cancer. Horm Cancer 6:120–127CrossRefPubMed
23.
Zurück zum Zitat Campbell JL, Elston FC, Blamey CW, Morris RW, Nicholson AH, Griffiths RI, Haybittle K (1981) Quantitative oestradiol receptor values in primary breast cancer and response of metastases to endocrine therapy. Lancet 2:1317–1319CrossRefPubMed Campbell JL, Elston FC, Blamey CW, Morris RW, Nicholson AH, Griffiths RI, Haybittle K (1981) Quantitative oestradiol receptor values in primary breast cancer and response of metastases to endocrine therapy. Lancet 2:1317–1319CrossRefPubMed
24.
Zurück zum Zitat Schooling CM (2016) Could androgens be relevant to partly explain why men have lower life expectancy than women? J Epidemiol Community Health 70(4):324–328CrossRefPubMed Schooling CM (2016) Could androgens be relevant to partly explain why men have lower life expectancy than women? J Epidemiol Community Health 70(4):324–328CrossRefPubMed
25.
Zurück zum Zitat Mayne BT, Bianco-miotto T, Buckberry S, Breen J, Clifton V, Shoubridge C, Roberts CT (2016) Large scale gene expression meta-analysis reveals expression in humans. Front Genet 7(183):1–14 Mayne BT, Bianco-miotto T, Buckberry S, Breen J, Clifton V, Shoubridge C, Roberts CT (2016) Large scale gene expression meta-analysis reveals expression in humans. Front Genet 7(183):1–14
26.
Zurück zum Zitat Cao S, Zhan Y, Dong Y (2016) Emerging data on androgen receptor splice variants in prostate cancer. Endocr Relat Cancer 23(12):199–210CrossRef Cao S, Zhan Y, Dong Y (2016) Emerging data on androgen receptor splice variants in prostate cancer. Endocr Relat Cancer 23(12):199–210CrossRef
Metadaten
Titel
Androgen Receptor and Ki67 Expression and Survival Outcomes in Non-small Cell Lung Cancer
verfasst von
Laurel Grant
Shantanu Banerji
Leigh Murphy
David E. Dawe
Craig Harlos
Yvonne Myal
Zoann Nugent
Anne Blanchard
Carla R. Penner
Gefei Qing
Marshall W. Pitz
Publikationsdatum
18.06.2018
Verlag
Springer US
Erschienen in
Discover Oncology / Ausgabe 4/2018
Print ISSN: 1868-8497
Elektronische ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-018-0336-7

Weitere Artikel der Ausgabe 4/2018

Discover Oncology 4/2018 Zur Ausgabe

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

03.05.2024 Mammakarzinom Nachrichten

Wenn bei Mammakarzinomen durch eine neoadjuvante Chemotherapie ein Downstaging von nodal-positiv zu nodal-negativ gelingt, scheint es auch ohne Axilladissektion nur selten zu axillären Rezidiven zu kommen.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärzte und Psychotherapeuten.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.