Immunohistochemical profiling of Bcl-2 and EGFR proteins in cervical carcinoma at a tertiary hospital in Ghana Bcl-2 and EGFR expression in cervical carcinoma
Main Article Content
Keywords
Cervical Cancer, EGFR, Bcl-2, Clinicopathological Characteristics, Tissue Microarray, Immunohistochemistry
Abstract
Background: Using Immunohistochemistry (IHC) to assess the expression of EGFR and Bcl-2, and their correlations with clinicopathological features in a cohort of cervical cancer cases.
Methodology: A retrospective and descriptive study in Komfo Anokye Teaching Hospital (KATH) Kumasi, Ghana. Patients were women diagnosed with cervical cancer at KATH from January 2015 to December 2016. For inclusion, suitable archived formalin fixed paraffin-embedded (FFPE) cases with adequately preserved tissue blocks and available clinicopathological data were selected for Tissue Microarray (TMA), otherwise, the cases were excluded. One hundred and thirty-five out of 230 cervical cases met the inclusion criteria. IHC assesses EGFR and Bcl-2 expressions, correlating with clinicopathological features in cervical cancer cases, enhancing molecular-clinical insights in the Ghanaian context.
Results: The mean age of the cases was 58.9 (SD ± 17.88). Predominantly, 96.3% of the cases were of the squamous cell carcinoma (SCC) subtype. The majority of the cases (49.63%) were grade III. EGFR and Bcl-2 were expressed in 35.2% and 25.7% of the cases, respectively. Neither EGFR nor Bcl-2 showed any significant correlation with age, subtype, and histological grade. Significant inverse correlation was, however, observed between EGFR and Bcl-2 expression (P<0.001).
Conclusion: The age stratification shown in this study confirms earlier reports of late age at diagnosis, mostly observed in our setting, and therefore emphasizes the need for effective and population-wide screening programs to ensure early diagnosis. The significant inverse correlation between EGFR and Bcl-2, suggestively leans towards a possible role played by EGFR in downregulating Bcl-2.
References
1. Anaman-Torgbor J, Angmorterh SK, Dordunoo D, Ofori EK: Cervical cancer screening behaviours and challenges: a sub-Saharan Africa perspective. Pan African Medical Journal 2020, 36.
2. Cao W, Qin K, Li F, Chen W: Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN). Journal of the National Cancer Center 2024, 4:128-34.
3. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2024, 74:229-63.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2021, 71:209-49.
5. Jedy-Agba E, Joko WY, Liu B, Buziba NG, Borok M, Korir A, Masamba L, Manraj SS, Finesse A, Wabinga H: Trends in cervical cancer incidence in sub-Saharan Africa. British journal of cancer 2020, 123:148-54.
6. Amoako YA, Awuah B, Larsen-Reindorf R, Awittor FK, Kyem G, Ofori-Boadu K, Osei-Bonsu E, Laryea DO: Malignant tumours in urban Ghana: evidence from the city of Kumasi. BMC cancer 2019, 19:1-12.
7. Tuck CZ, Cooper R, Aryeetey R, Gray LA, Akparibo R: A critical review and analysis of the context, current burden, and application of policy to improve cancer equity in Ghana. International Journal for Equity in Health 2023, 22:254.
8. Calys-Tagoe BN, Aheto JM, Mensah G, Biritwum RB, Yawson AE: Cervical cancer screening practices among women in Ghana: evidence from wave 2 of the WHO study on global AGEing and adult health. BMC women's health 2020, 20:1-9.
9. Obafemi F, Umahi-Ottah G: A review of global Cancer prevalence and therapy. J Cancer Res Treat Prev 2023, 1:128-47.
10. Momenimovahed Z, Salehiniya H: Incidence, mortality and risk factors of cervical cancer in the world. Biomedical Research and Therapy 2017, 4:1795-811.
11. Bruni L, Diaz M, Castellsagué M, Ferrer E, Bosch FX, de Sanjosé S: Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. Journal of Infectious Diseases 2010, 202:1789-99.
12. Balasubramaniam SD, Balakrishnan V, Oon CE, Kaur G: Key molecular events in cervical cancer development. Medicina 2019, 55:384.
13. Dasari S, Wudayagiri R, Valluru L: Cervical cancer: Biomarkers for diagnosis and treatment. Clinica chimica acta 2015, 445:7-11.
14. Volkova LV, Pashov AI, Omelchuk NN: Cervical carcinoma: oncobiology and biomarkers. International journal of molecular sciences 2021, 22:12571.
15. Shukla S, Dass J, Pujani M: p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18. South Asian Journal of Cancer 2014, 3:48.
16. Chung C: Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation–positive non-small cell lung cancers: an update for recent advances in therapeutics. Journal of Oncology Pharmacy Practice 2016, 22:461-76.
17. Wei H, Wang X, Chen K, Ling S, Yi C: Analysis of gene mutation associated with tyrosine kinase inhibitor sensitivity of epidermal growth factor receptor in cervical cancer patients. European Review for Medical & Pharmacological Sciences 2018, 22.
18. Ukirde R, Sawant R, Nerkar A: Role of Epidermal Growth Factor Receptor Inhibitors in Treating Cancer. Curr Trends Pharm Pharm Chem 2020, 2:57-63.
19. Rajaram P, Chandra P, Ticku S, Pallavi B, Rudresh K, Mansabdar P: Epidermal growth factor receptor: Role in human cancer. Indian Journal of Dental Research 2017, 28:687-94.
20. Maennling AE, Tur MK, Niebert M, Klockenbring T, Zeppernick F, Gattenlöhner S, Meinhold-Heerlein I, Hussain AF: Molecular targeting therapy against EGFR family in breast cancer: progress and future potentials. Cancers 2019, 11:1826.
21. Tomuleasa C, Tigu A-B, Munteanu R, Moldovan C-S, Kegyes D, Onaciu A, Gulei D, Ghiaur G, Einsele H, Croce CM: Therapeutic advances of targeting receptor tyrosine kinases in cancer. Signal Transduction and Targeted Therapy 2024, 9:201.
22. Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N, Committee EG: Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2017, 28:iv72-iv83.
23. Opoku F, Bedu-Addo K, Titiloye NA, Atta Manu E, Ameh-Mensah C, Duduyemi BM: Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana. Plos one 2021, 16:e0258543.
24. Tarakji B, Kujan O, Nassani MZ: Immunohistochemical expression of p53 in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Journal of cancer epidemiology 2010, 2010:250606.
25. Awua A, Sackey S, Osei Y, Asmah R, Wiredu E: Prevalence of human papillomavirus genotypes among women with cervical cancer in Ghana. Infectious agents and cancer 2016, 11:1-9.
26. Titiloye NA, Okai I, Duduyemi BM: Histopathological features of Cervical Cancer in a Tertiary Hospital in Kumasi Ghana: a 9 year retrospective study. Journal of Medical and Biomedical Sciences 2020, 7:19-23.
27. Ebu NI, Amissah-Essel S, Asiedu C, Akaba S, Pereko KA: Impact of health education intervention on knowledge and perception of cervical cancer and screening for women in Ghana. BMC public health 2019, 19:1-11.
28. Nartey Y, Hill PC, Amo-Antwi K, Nyarko KM, Yarney J, Cox B: Factors contributing to the low survival among women with a diagnosis of invasive cervical cancer in Ghana. International Journal of Gynecological Cancer 2017, 27:1926-34.
29. Der E, Adu-Bonsaffoh K, Tettey Y, Kwame-Aryee R, Seffah J, Alidu H, Gyasi R: Clinico-pathological characteristics of cervical cancer in Ghanaian women. Journal of Medical and Biomedical sciences 2014, 3:27-32.
30. Keshinro S, Nwafor C, Oshun P: Histologic analysis of gynaecologic lesions in Nigerians. East African Medical Journal 2015, 92:245-52.
31. Omenai SA, Ajani MA, Okolo CA: Histopathological characteristics of carcinoma of the uterine cervix in a tertiary hospital in southern Nigeria. Sahel Medical Journal 2020, 23:158-63.
32. Rayis DA, Zulfu A, Yassin K, Merghani A, Fagiri AA, Raheem SA: Histopathological pattern of gynaecological malignancies: National Health Laboratory (NHL), Sudan. GPH—International Journal of Health Sciences and Nursing [Internet] 2018.
33. Barquet-Muñoz SA, Cruz-Rodríguez E, De León DFC, Isla-Ortiz D, Montalvo-Esquivel G, Herrera-Montalvo LA, Pérez-Plasencia C, Pérez-Montiel D, Herrera-Gómez Á: Histology as prognostic factor in early-stage cervical carcinoma. Experience in a third-level institution. Revista de investigación clínica 2017, 69:286-92.
34. Small Jr W, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN: Cervical cancer: a global health crisis. Cancer 2017, 123:2404-12.
35. Zhang S, Xu H, Zhang L, Qiao Y: Cervical cancer: Epidemiology, risk factors and screening. Chinese Journal of Cancer Research 2020, 32:720.
36. Yin K-C, Lu C-H, Lin J-C, Hsu C-Y, Wang L: Treatment outcomes of locally advanced cervical cancer by histopathological types in a single institution: A propensity score matching study. Journal of the Formosan Medical Association 2018, 117:922-31.
37. Giannella L, Di Giuseppe J, Delli Carpini G, Grelloni C, Fichera M, Sartini G, Caimmi S, Natalini L, Ciavattini A: HPV-negative adenocarcinomas of the uterine cervix: from molecular characterization to clinical implications. International Journal of Molecular Sciences 2022, 23:15022.
38. Gien LT, Beauchemin M-C, Thomas G: Adenocarcinoma: a unique cervical cancer. Gynecologic oncology 2010, 116:140-6.
39. Cao L, Wen H, Feng Z, Han X, Wu X: Distinctive clinicopathologic characteristics and prognosis for different histologic subtypes of early cervical cancer. International Journal of Gynecological Cancer 2019, 29:1244-51.
40. Mabuchi S, Okazawa M, Matsuo K, Kawano M, Suzuki O, Miyatake T, Enomoto T, Kamiura S, Ogawa K, Kimura T: Impact of histological subtype on survival of patients with surgically-treated stage IA2–IIB cervical cancer: adenocarcinoma versus squamous cell carcinoma. Gynecologic Oncology 2012, 127:114-20.
41. Hu K, Wang W, Liu X, Meng Q, Zhang F: Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma of cervix after definitive radiotherapy or concurrent chemoradiotherapy. Radiation Oncology 2018, 13:1-7.
42. Meng Y, Chu T, Lin S, Wu P, Zhi W, Peng T, Ding W, Luo D, Wu P: Clinicopathological characteristics and prognosis of cervical cancer with different histological types: a population-based cohort study. Gynecologic Oncology 2021, 163:545-51.
43. Usman M, Otene S: Clinicopathologic Features of Cervical Cancer Patients seen in a Comprehensive Cancer Centre in North-Western Nigeria. Open Journal of Medical Research (ISSN: 2734-2093) 2021, 2:56–65-56–65.
44. Iida K, Nakayama K, Rahman M, Rahman M, Ishikawa M, Katagiri A, Yeasmin S, Otsuki Y, Kobayashi H, Nakayama S: EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target. British journal of cancer 2011, 105:420-7.
45. Soonthornthum T, Arias-Pulido H, Joste N, Lomo L, Muller C, Rutledge T, Verschraegen C: Epidermal growth factor receptor as a biomarker for cervical cancer. Annals of oncology 2011, 22:2166-78.
46. Cerciello F, Riesterer O, Sherweif M, Odermatt B, Ciernik IF: Is EGFR a moving target during radiotherapy of carcinoma of the uterine cervix? Gynecologic oncology 2007, 106:394-9.
47. Baltazar F, Longatto Filho A, Pinheiro C, Moreira MA, Queiroz GS, Oton GJB, Júnior AF, Ribeiro LFJ, Schmitt FC: Cyclooxygenase-2 and epidermal growth factor receptor expressions in different histological subtypes of cervical carcinomas. International journal of gynecological pathology 2007, 26:235-41.
48. Longatto-Filho A, Pinheiro C, Martinho O, Moreira MA, Ribeiro LF, Queiroz GS, Schmitt FC, Baltazar F, Reis RM: Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma. BMC cancer 2009, 9:1-8.
49. Cho NH, Kim YB, Park TK, Kim GE, Park K, Song KJ: P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma. Gynecologic oncology 2003, 91:346-53.
50. Kim GE, Kim YB, Cho NH, Chung H-C, Pyo HR, Lee JD, Park TK, Koom WS, Chun M, Suh CO: Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival. Clinical Cancer Research 2004, 10:1366-74.
51. Kersemaekers A-MF, Fleuren GJ, Kenter GG, Van den Broek LJ, Uljee SM, Hermans J, Van de Vijver MJ: Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clinical Cancer Research 1999, 5:577-86.
52. Gur C, Kandemir FM, Caglayan C, Satıcı E: Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways. Chemico-biological interactions 2022, 365:110073.
53. Radha G, Raghavan SC: BCL2: A promising cancer therapeutic target. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2017, 1868:309-14.
54. Abdul Rahman SF, Xiang Lian BS, Mohana-Kumaran N: Targeting the B-cell lymphoma 2 anti-apoptotic proteins for cervical cancer treatment. Future Oncology 2020, 16:2235-49.
55. Munakata S, Watanabe O, Ohashi K, Morino H: Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance. American journal of clinical pathology 2005, 123:879-85.
56. Wootipoom V, Lekhyananda N, Phungrassami T, Boonyaphiphat P, Thongsuksai P: Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy. Gynecologic oncology 2004, 94:636-42.
57. Babiker AY, Almatroudi A, Allemailem KS, Husain NEO, Alsammani MA, Alsahli MA, Rahmani AH: Clinicopathologic aspects of squamous cell carcinoma of the uterine cervix: role of PTEN, BCL2 and P53. Applied Sciences 2018, 8:2124.
58. Jain D, Srinivasan R, Patel FD, Gupta SK: Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical carcinoma stage IIb/III patients treated by radiotherapy. Gynecologic oncology 2003, 88:22-8.
59. Grace VB, Shalini JV, Devaraj SN, Devaraj H: Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆. Gynecologic oncology 2003, 91:51-8.
60. Protrka Z, Djuric J, Protrka O, Arsenijevic S: The possible role of bcl-2 expression of tumors of the uterine cervix. J BUON 2010, 15:323-9.
61. Zhou X, Wang M: Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis. Genet Mol Res 2015, 14:17059-67.
62. Alam M, Alam S, Shamsi A, Adnan M, Elasbali AM, Al-Soud WA, Alreshidi M, Hawsawi YM, Tippana A, Pasupuleti VR: Bax/Bcl-2 cascade is regulated by the EGFR pathway: therapeutic targeting of non-small cell lung cancer. Frontiers in Oncology 2022, 12:869672.
63. RD L: bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer 1994, 69:135-9.
2. Cao W, Qin K, Li F, Chen W: Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN). Journal of the National Cancer Center 2024, 4:128-34.
3. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2024, 74:229-63.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2021, 71:209-49.
5. Jedy-Agba E, Joko WY, Liu B, Buziba NG, Borok M, Korir A, Masamba L, Manraj SS, Finesse A, Wabinga H: Trends in cervical cancer incidence in sub-Saharan Africa. British journal of cancer 2020, 123:148-54.
6. Amoako YA, Awuah B, Larsen-Reindorf R, Awittor FK, Kyem G, Ofori-Boadu K, Osei-Bonsu E, Laryea DO: Malignant tumours in urban Ghana: evidence from the city of Kumasi. BMC cancer 2019, 19:1-12.
7. Tuck CZ, Cooper R, Aryeetey R, Gray LA, Akparibo R: A critical review and analysis of the context, current burden, and application of policy to improve cancer equity in Ghana. International Journal for Equity in Health 2023, 22:254.
8. Calys-Tagoe BN, Aheto JM, Mensah G, Biritwum RB, Yawson AE: Cervical cancer screening practices among women in Ghana: evidence from wave 2 of the WHO study on global AGEing and adult health. BMC women's health 2020, 20:1-9.
9. Obafemi F, Umahi-Ottah G: A review of global Cancer prevalence and therapy. J Cancer Res Treat Prev 2023, 1:128-47.
10. Momenimovahed Z, Salehiniya H: Incidence, mortality and risk factors of cervical cancer in the world. Biomedical Research and Therapy 2017, 4:1795-811.
11. Bruni L, Diaz M, Castellsagué M, Ferrer E, Bosch FX, de Sanjosé S: Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. Journal of Infectious Diseases 2010, 202:1789-99.
12. Balasubramaniam SD, Balakrishnan V, Oon CE, Kaur G: Key molecular events in cervical cancer development. Medicina 2019, 55:384.
13. Dasari S, Wudayagiri R, Valluru L: Cervical cancer: Biomarkers for diagnosis and treatment. Clinica chimica acta 2015, 445:7-11.
14. Volkova LV, Pashov AI, Omelchuk NN: Cervical carcinoma: oncobiology and biomarkers. International journal of molecular sciences 2021, 22:12571.
15. Shukla S, Dass J, Pujani M: p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18. South Asian Journal of Cancer 2014, 3:48.
16. Chung C: Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation–positive non-small cell lung cancers: an update for recent advances in therapeutics. Journal of Oncology Pharmacy Practice 2016, 22:461-76.
17. Wei H, Wang X, Chen K, Ling S, Yi C: Analysis of gene mutation associated with tyrosine kinase inhibitor sensitivity of epidermal growth factor receptor in cervical cancer patients. European Review for Medical & Pharmacological Sciences 2018, 22.
18. Ukirde R, Sawant R, Nerkar A: Role of Epidermal Growth Factor Receptor Inhibitors in Treating Cancer. Curr Trends Pharm Pharm Chem 2020, 2:57-63.
19. Rajaram P, Chandra P, Ticku S, Pallavi B, Rudresh K, Mansabdar P: Epidermal growth factor receptor: Role in human cancer. Indian Journal of Dental Research 2017, 28:687-94.
20. Maennling AE, Tur MK, Niebert M, Klockenbring T, Zeppernick F, Gattenlöhner S, Meinhold-Heerlein I, Hussain AF: Molecular targeting therapy against EGFR family in breast cancer: progress and future potentials. Cancers 2019, 11:1826.
21. Tomuleasa C, Tigu A-B, Munteanu R, Moldovan C-S, Kegyes D, Onaciu A, Gulei D, Ghiaur G, Einsele H, Croce CM: Therapeutic advances of targeting receptor tyrosine kinases in cancer. Signal Transduction and Targeted Therapy 2024, 9:201.
22. Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N, Committee EG: Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2017, 28:iv72-iv83.
23. Opoku F, Bedu-Addo K, Titiloye NA, Atta Manu E, Ameh-Mensah C, Duduyemi BM: Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana. Plos one 2021, 16:e0258543.
24. Tarakji B, Kujan O, Nassani MZ: Immunohistochemical expression of p53 in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Journal of cancer epidemiology 2010, 2010:250606.
25. Awua A, Sackey S, Osei Y, Asmah R, Wiredu E: Prevalence of human papillomavirus genotypes among women with cervical cancer in Ghana. Infectious agents and cancer 2016, 11:1-9.
26. Titiloye NA, Okai I, Duduyemi BM: Histopathological features of Cervical Cancer in a Tertiary Hospital in Kumasi Ghana: a 9 year retrospective study. Journal of Medical and Biomedical Sciences 2020, 7:19-23.
27. Ebu NI, Amissah-Essel S, Asiedu C, Akaba S, Pereko KA: Impact of health education intervention on knowledge and perception of cervical cancer and screening for women in Ghana. BMC public health 2019, 19:1-11.
28. Nartey Y, Hill PC, Amo-Antwi K, Nyarko KM, Yarney J, Cox B: Factors contributing to the low survival among women with a diagnosis of invasive cervical cancer in Ghana. International Journal of Gynecological Cancer 2017, 27:1926-34.
29. Der E, Adu-Bonsaffoh K, Tettey Y, Kwame-Aryee R, Seffah J, Alidu H, Gyasi R: Clinico-pathological characteristics of cervical cancer in Ghanaian women. Journal of Medical and Biomedical sciences 2014, 3:27-32.
30. Keshinro S, Nwafor C, Oshun P: Histologic analysis of gynaecologic lesions in Nigerians. East African Medical Journal 2015, 92:245-52.
31. Omenai SA, Ajani MA, Okolo CA: Histopathological characteristics of carcinoma of the uterine cervix in a tertiary hospital in southern Nigeria. Sahel Medical Journal 2020, 23:158-63.
32. Rayis DA, Zulfu A, Yassin K, Merghani A, Fagiri AA, Raheem SA: Histopathological pattern of gynaecological malignancies: National Health Laboratory (NHL), Sudan. GPH—International Journal of Health Sciences and Nursing [Internet] 2018.
33. Barquet-Muñoz SA, Cruz-Rodríguez E, De León DFC, Isla-Ortiz D, Montalvo-Esquivel G, Herrera-Montalvo LA, Pérez-Plasencia C, Pérez-Montiel D, Herrera-Gómez Á: Histology as prognostic factor in early-stage cervical carcinoma. Experience in a third-level institution. Revista de investigación clínica 2017, 69:286-92.
34. Small Jr W, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN: Cervical cancer: a global health crisis. Cancer 2017, 123:2404-12.
35. Zhang S, Xu H, Zhang L, Qiao Y: Cervical cancer: Epidemiology, risk factors and screening. Chinese Journal of Cancer Research 2020, 32:720.
36. Yin K-C, Lu C-H, Lin J-C, Hsu C-Y, Wang L: Treatment outcomes of locally advanced cervical cancer by histopathological types in a single institution: A propensity score matching study. Journal of the Formosan Medical Association 2018, 117:922-31.
37. Giannella L, Di Giuseppe J, Delli Carpini G, Grelloni C, Fichera M, Sartini G, Caimmi S, Natalini L, Ciavattini A: HPV-negative adenocarcinomas of the uterine cervix: from molecular characterization to clinical implications. International Journal of Molecular Sciences 2022, 23:15022.
38. Gien LT, Beauchemin M-C, Thomas G: Adenocarcinoma: a unique cervical cancer. Gynecologic oncology 2010, 116:140-6.
39. Cao L, Wen H, Feng Z, Han X, Wu X: Distinctive clinicopathologic characteristics and prognosis for different histologic subtypes of early cervical cancer. International Journal of Gynecological Cancer 2019, 29:1244-51.
40. Mabuchi S, Okazawa M, Matsuo K, Kawano M, Suzuki O, Miyatake T, Enomoto T, Kamiura S, Ogawa K, Kimura T: Impact of histological subtype on survival of patients with surgically-treated stage IA2–IIB cervical cancer: adenocarcinoma versus squamous cell carcinoma. Gynecologic Oncology 2012, 127:114-20.
41. Hu K, Wang W, Liu X, Meng Q, Zhang F: Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma of cervix after definitive radiotherapy or concurrent chemoradiotherapy. Radiation Oncology 2018, 13:1-7.
42. Meng Y, Chu T, Lin S, Wu P, Zhi W, Peng T, Ding W, Luo D, Wu P: Clinicopathological characteristics and prognosis of cervical cancer with different histological types: a population-based cohort study. Gynecologic Oncology 2021, 163:545-51.
43. Usman M, Otene S: Clinicopathologic Features of Cervical Cancer Patients seen in a Comprehensive Cancer Centre in North-Western Nigeria. Open Journal of Medical Research (ISSN: 2734-2093) 2021, 2:56–65-56–65.
44. Iida K, Nakayama K, Rahman M, Rahman M, Ishikawa M, Katagiri A, Yeasmin S, Otsuki Y, Kobayashi H, Nakayama S: EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target. British journal of cancer 2011, 105:420-7.
45. Soonthornthum T, Arias-Pulido H, Joste N, Lomo L, Muller C, Rutledge T, Verschraegen C: Epidermal growth factor receptor as a biomarker for cervical cancer. Annals of oncology 2011, 22:2166-78.
46. Cerciello F, Riesterer O, Sherweif M, Odermatt B, Ciernik IF: Is EGFR a moving target during radiotherapy of carcinoma of the uterine cervix? Gynecologic oncology 2007, 106:394-9.
47. Baltazar F, Longatto Filho A, Pinheiro C, Moreira MA, Queiroz GS, Oton GJB, Júnior AF, Ribeiro LFJ, Schmitt FC: Cyclooxygenase-2 and epidermal growth factor receptor expressions in different histological subtypes of cervical carcinomas. International journal of gynecological pathology 2007, 26:235-41.
48. Longatto-Filho A, Pinheiro C, Martinho O, Moreira MA, Ribeiro LF, Queiroz GS, Schmitt FC, Baltazar F, Reis RM: Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma. BMC cancer 2009, 9:1-8.
49. Cho NH, Kim YB, Park TK, Kim GE, Park K, Song KJ: P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma. Gynecologic oncology 2003, 91:346-53.
50. Kim GE, Kim YB, Cho NH, Chung H-C, Pyo HR, Lee JD, Park TK, Koom WS, Chun M, Suh CO: Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival. Clinical Cancer Research 2004, 10:1366-74.
51. Kersemaekers A-MF, Fleuren GJ, Kenter GG, Van den Broek LJ, Uljee SM, Hermans J, Van de Vijver MJ: Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clinical Cancer Research 1999, 5:577-86.
52. Gur C, Kandemir FM, Caglayan C, Satıcı E: Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways. Chemico-biological interactions 2022, 365:110073.
53. Radha G, Raghavan SC: BCL2: A promising cancer therapeutic target. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2017, 1868:309-14.
54. Abdul Rahman SF, Xiang Lian BS, Mohana-Kumaran N: Targeting the B-cell lymphoma 2 anti-apoptotic proteins for cervical cancer treatment. Future Oncology 2020, 16:2235-49.
55. Munakata S, Watanabe O, Ohashi K, Morino H: Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance. American journal of clinical pathology 2005, 123:879-85.
56. Wootipoom V, Lekhyananda N, Phungrassami T, Boonyaphiphat P, Thongsuksai P: Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy. Gynecologic oncology 2004, 94:636-42.
57. Babiker AY, Almatroudi A, Allemailem KS, Husain NEO, Alsammani MA, Alsahli MA, Rahmani AH: Clinicopathologic aspects of squamous cell carcinoma of the uterine cervix: role of PTEN, BCL2 and P53. Applied Sciences 2018, 8:2124.
58. Jain D, Srinivasan R, Patel FD, Gupta SK: Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical carcinoma stage IIb/III patients treated by radiotherapy. Gynecologic oncology 2003, 88:22-8.
59. Grace VB, Shalini JV, Devaraj SN, Devaraj H: Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆. Gynecologic oncology 2003, 91:51-8.
60. Protrka Z, Djuric J, Protrka O, Arsenijevic S: The possible role of bcl-2 expression of tumors of the uterine cervix. J BUON 2010, 15:323-9.
61. Zhou X, Wang M: Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis. Genet Mol Res 2015, 14:17059-67.
62. Alam M, Alam S, Shamsi A, Adnan M, Elasbali AM, Al-Soud WA, Alreshidi M, Hawsawi YM, Tippana A, Pasupuleti VR: Bax/Bcl-2 cascade is regulated by the EGFR pathway: therapeutic targeting of non-small cell lung cancer. Frontiers in Oncology 2022, 12:869672.
63. RD L: bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer 1994, 69:135-9.
Article Sidebar
Article Details
How to Cite
Duduyemi, B., Addae , E. K., Opoku , F., & Bedu-Addo, K. Immunohistochemical profiling of Bcl-2 and EGFR proteins in cervical carcinoma at a tertiary hospital in Ghana: Bcl-2 and EGFR expression in cervical carcinoma. Nigerian Medical Journal, 66(2), 198–208. https://doi.org/10.71480/nmj.v66i2.713
Section
Original Articles
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
This is an open-access journal and articles are distributed under the terms of the Creative Commons Attribution Non-Commercial Share-Alike License 4.0. This licence allows users to download and share, remix, tweak and build upon the article for non-commercial purposes, so long as the original authorship is acknowledged and the new creations are licensed under identical terms.