Prognostic Importance of Ki-67 Expression in Early-Stage Glottic Larynx Cancer Treated with Radiotherapy
Abstract
Objective: The prognostic importance of Ki-67 expression in early-stage glottic larynx cancer is controversial. In this study, we aimed to evaluate the prognostic importance of Ki-67 expression in early-stage glottic cancer treated with curative radiotherapy at a single centre.
Material and Method: Between 2010 and 2021, patients with T1a/bN0 stage glottic larynx cancer treated with curative radiotherapy were identified. The cases included in this study were re-evaluated by a single pathologist retrospectively. According to the ROC curve, the optimal cut-off value was 35% for Ki-67. Above these cut-off points were accepted as high expression levels (Ki-67-high), while below these points were accepted as low expression levels (Ki-67-low).
Results: A total of 49 patients with early-stage glottic larynx cancer treated with definitive radiotherapy were included. The median follow-up time was 35.74 (range; 7.03-161.65) months. The median OS was 95.4 (range; 62.1-128.8) months. According to univariate analysis, tumour grade (p=0.006) and Ki-67 expression level (low vs high; p=0.039) were the prognostic factors that predict OS. The median DFS was 42.1 (range; 32.8-51.3) months. According to univariate analyses, tumour grade (p=0.008) and Ki-67 expression level (low vs high; p=0.007) were the prognostic factors that predict DFS.
Conclusion: Higher Ki-67 expression was associated with lower OS and DFS. Ki-67 expression level can be used as a biomarker to determine treatment choice in these patients. Additional prospective studies with more patients are needed to confirm our results.
Keywords
Supporting Institution
none
References
- Williamson AJ, Bondje S. Glottic Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 18, 2022. google scholar
- Cenik Z, Uyar Y, Ozer B, Bulun E. Surgical Treatment in Larynx Cancer. Selcuk Tıp Dergisi 1994;10(2):151-6. google scholar
- Mucha-Małecka A, Chrostowska A, Urbanek K, Małecki K. Prognostic factors in patients with T1 glottic cancer treated with radiotherapy. Strahlenther Onkol 2019;195(9):792-804. google scholar
- Pakkanen P, Irjala H, Ilmarinen T, Halme E, Lindholm P, Mäkitie A, et al. Survival and Larynx Preservation in Early Glottic Cancer: A Randomized Trial Comparing Laser Surgery and Radiation Therapy. Int J Radiat Oncol Biol Phys 2022;113(1):96-100. google scholar
- Kanyılmaz G, Yavuz BB, Aktan M, Karaağaç M, Uyar M, Fındık S. Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors. Eur J Breast Health 2019;15(4):256-61. google scholar
- Dumitru CS, Ceausu AR, Comsa S, Raica M. Loss of E-Cadherin Expression Correlates With Ki-67 in Head and Neck Squamous Cell Carcinoma. In Vivo 2022;36(3):1150-54. google scholar
- Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67(2):93-9. google scholar
- College of American Pathologist. Available from: URL: http://www. cap. org. (Accessed 2022 September 24). google scholar
- Kop E, de Bock GH, Noordhuis MG, Slagter-Menkema L, van der Laan BFAM, Langendijk JA, et al. Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy. Clin Otolaryngol 2020;45(1):12-20. google scholar
- Cavaliere M, Bisogno A, Scarpa A, D’Urso A, Marra P, Colacurcio V, et al. Biomarkers of laryngeal squamous cell carcinoma: a review. Ann Diagn Pathol 2021;54:151787. google scholar
- Gioacchini FM, Alicandri-Ciufelli M, Magliulo G, Rubini C, Presutti L, Re M. The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2015;272(7):1569-76. google scholar
- Kropveld A, Slootweg PJ, Blankenstein MA, Terhaard CH, Hordijk GJ. Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 1998;108(10):1548-52. google scholar
- Ahmed WA, Suzuki K, Imaeda Y, Horibe Y. Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy. Auris Nasus Larynx 2008;35(2):213-19. google scholar
- Sakata K, Oouchi A, Nagakura H, Akiba H, Tamakawa M, Koito K, et al. Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index. Int J Radiat Oncol Biol Phys 2000;47(1):81-8. google scholar
- Nichols AC, Whelan F, Basmaji J, Dhaliwal S, Dowthwaite S, Chapeskie C, et al. Ki-67 expression predicts radiotherapy failure in early glottic cancer. J Otolaryngol Head Neck Surg 2012;41(2):124-30. google scholar
- Lavertu P, Adelstein DJ, Myles J, Secic M. P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope 2001;111(11):1878-92. google scholar
- Agrawal N, Ha PK. Management of early-stage laryngeal cancer. Otolaryngol Clin North Am. 2008;41(4):757-vii. google scholar
Küratif Radyoterapi ile Tedavi Edilmiş Erken Evre Glottik Larinks Kanserinde Ki-67'nin Prognostik Önemi
Abstract
Amaç: Erken evre glottik larinks kanserinde Ki-67 ekspresyonunun prognostik önemi halen tartışmalıdır. Bu çalışmada küratif radyoterapi ile tedavi edilmiş erken evre glottik larinks kanserde Ki-67 ekspresyonunun prognostik önemini değerlendirmek amaçlanmıştır.
Metod: 2010-2021 yılları arasında kliniğimizde küratif radyoterapi ile tedavi edilmiş T1a/bN0 hastalar tespit edildikten sonra olgular geriye dönük olarak tek bir patolog tarafından Ki-67 ekspresyonu açısından yeniden değerlendirilmiştir. ROC eğrisine göre Ki-67 için optimal cut-off değeri %35 tespit edilmesi nedeniyle bu eşik noktasının üstü yüksek ekspresyon (Ki-67-yüksek), altı ise düşük ekspresyon (Ki-67-düşük) olarak kabul edilmiştir.
Bulgular: Küratif radyoterapi ile tedavi edilmiş toplam 49 hasta analize dahil edildi. Ortanca takip süresi 35,74 (7,03-161,65) ay idi. Ortanca genel sağkalım süresi (GS) 95,4 (62,1-128,8) ay idi. Tek değişkenli analize göre, tümör gradı (p=0.006) ve Ki-67 ekspresyon düzeyi (p=0.039) GS’yi öngören anlamlı prognostik faktörler olarak saptandı. Ortanca hastalıksız sağkalım süresi (HSS) 42,1 (32,8-51,3) ay idi. Tek değişkenli analizlere göre, tümör gradı (p=0.008) ve Ki-67 ekspresyon düzeyi (p=0.007), HSS’yi öngören anlamlı prognostik faktörler olarak bulundu.
Sonuç: Ki-67 ekspresyonu sağkalımı öngörebilecek prognostik bir belirteç olarak bulunmuş olup yüksek ekspresyon düzeyi daha düşük GS ve HSS ile ilişkilendirilmiştir. Ki-67 ekspresyon seviyesi, bu hastalarda tedavi seçimini belirlemek için bir biyobelirteç olarak kullanılabilir. Sonuçlarımızı doğrulamak için daha fazla hasta ile ek prospektif çalışmalara ihtiyaç vardır.
References
- Williamson AJ, Bondje S. Glottic Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 18, 2022. google scholar
- Cenik Z, Uyar Y, Ozer B, Bulun E. Surgical Treatment in Larynx Cancer. Selcuk Tıp Dergisi 1994;10(2):151-6. google scholar
- Mucha-Małecka A, Chrostowska A, Urbanek K, Małecki K. Prognostic factors in patients with T1 glottic cancer treated with radiotherapy. Strahlenther Onkol 2019;195(9):792-804. google scholar
- Pakkanen P, Irjala H, Ilmarinen T, Halme E, Lindholm P, Mäkitie A, et al. Survival and Larynx Preservation in Early Glottic Cancer: A Randomized Trial Comparing Laser Surgery and Radiation Therapy. Int J Radiat Oncol Biol Phys 2022;113(1):96-100. google scholar
- Kanyılmaz G, Yavuz BB, Aktan M, Karaağaç M, Uyar M, Fındık S. Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors. Eur J Breast Health 2019;15(4):256-61. google scholar
- Dumitru CS, Ceausu AR, Comsa S, Raica M. Loss of E-Cadherin Expression Correlates With Ki-67 in Head and Neck Squamous Cell Carcinoma. In Vivo 2022;36(3):1150-54. google scholar
- Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67(2):93-9. google scholar
- College of American Pathologist. Available from: URL: http://www. cap. org. (Accessed 2022 September 24). google scholar
- Kop E, de Bock GH, Noordhuis MG, Slagter-Menkema L, van der Laan BFAM, Langendijk JA, et al. Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy. Clin Otolaryngol 2020;45(1):12-20. google scholar
- Cavaliere M, Bisogno A, Scarpa A, D’Urso A, Marra P, Colacurcio V, et al. Biomarkers of laryngeal squamous cell carcinoma: a review. Ann Diagn Pathol 2021;54:151787. google scholar
- Gioacchini FM, Alicandri-Ciufelli M, Magliulo G, Rubini C, Presutti L, Re M. The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2015;272(7):1569-76. google scholar
- Kropveld A, Slootweg PJ, Blankenstein MA, Terhaard CH, Hordijk GJ. Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 1998;108(10):1548-52. google scholar
- Ahmed WA, Suzuki K, Imaeda Y, Horibe Y. Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy. Auris Nasus Larynx 2008;35(2):213-19. google scholar
- Sakata K, Oouchi A, Nagakura H, Akiba H, Tamakawa M, Koito K, et al. Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index. Int J Radiat Oncol Biol Phys 2000;47(1):81-8. google scholar
- Nichols AC, Whelan F, Basmaji J, Dhaliwal S, Dowthwaite S, Chapeskie C, et al. Ki-67 expression predicts radiotherapy failure in early glottic cancer. J Otolaryngol Head Neck Surg 2012;41(2):124-30. google scholar
- Lavertu P, Adelstein DJ, Myles J, Secic M. P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope 2001;111(11):1878-92. google scholar
- Agrawal N, Ha PK. Management of early-stage laryngeal cancer. Otolaryngol Clin North Am. 2008;41(4):757-vii. google scholar
Details
| Primary Language | English |
|---|---|
| Subjects | Otorhinolaryngology |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | October 4, 2023 |
| Submission Date | March 28, 2023 |
| Published in Issue | Year 2023 |