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The Professional Medical Journal www.theprofesional.com ORIGINAL PROF-2432

TUMOR MARKERS; Efficacy of CA-125, CEA, AFP, & Beta HCG An institutional based descriptive & prospective study in diagnosis of ovarian

Dr. Naseer Ahmed Shaikh1, Dr. Farzana Memon2, Dr. Rukhsana Parveen Samo3 1. Assistant Professor LUMHS Jamshoro ABSTRACT… Object: Analysis of serum tumor markers CA-125, CEA, AFP, & ß-HCG in patients 2. Associate Professor with ovarian malignant tumors and correlation of their serum levels with histological types. Study LUMHS Jamshoro 3. Senior Lecturer Design: Institution based descriptive and prospective study. Place & Duration: Department of LUMHS Jamshoro , Liaquat University of Medical & Health Sciences, Jamshoro from January 2009 to June 2011. Material & Methods: One hundred cases, diagnosed as ovarian malignant tumor on H&E were selected for study & measurement of serum CA-125, CEA, AFP, & ß-HCG preoperatively and postoperatively in each case. Results: Out of 100 ovarian diagnosed on H&E stain 33 were serous , 29 mucinous , 19 germ cell tumors and 15 sex-cord stromal tumors, 1 endometroid , 1 brenner tumor, 1 clear cell carcinoma and 1 case of NHL. Increased level of CA-125 was seen preoperatively in 33/33 cases Correspondence Address: Dr. Naseer Ahmed Shaikh of serous cystadenocarcinoma and 24/29 cases of mucinous adenocarcinoma. Surprisingly D/44, 2179, Bachal Shah Incline increased levels were also seen in 10/19 and 8/15 in sex-cord stromal tumors. Hyderabad. Sindh. CEA is raised in mucinous tumors. AFP & ß-HCG were raised in germ cell tumors & sex cord- [email protected] stromal tumors. Serum levels were declined following appropriate therapy of the tumors. Conclusions: Serum tumor markers are useful and important for the detection of ovarian tumors. They may also help in assessment of response to specific treatment, prognosis & follow up of patient.

Key words: CA-125, (CEA), Alpha fetaprotein (AFP) Article received on: 06/02/2014 Accepted for Publication: Article Citation: Shaikh NA, Memon F, Samo RP. Tumor markers; efficacy of CA-125, CEA, AFP, 16/05/2014 & Beta HCG. An institutional based descriptive & prospective study in Received after proof reading: 16/08/2014 diagnosis of ovarian malignancy. Professional Med J 2014;21(4):621-627.

INTRODUCTION incidence & mortality is generally lower for Asian & Ovarian posed the greatest challenge African countraries6. is 2nd to 4th amongst gynecological malignancy. It is 2nd most most common leading cause of death from common malignancy in female reproductive gynecologic malignancy in Pakistan. Its mortality system1. The worldwide incidence of ovarian ranks 2nd to 5th in various studies7,8,9,10. In United cancer is 192.4, mortality 114.2, & prevalence is States it accounts for 4% of all cancers in women & 507.5 per 100,000 persons per year2. Incidence 5% of estimated cancer deaths11. has been rising about 1-2% per year in several countries3. A female’s risk at birth of having ovarian Epithelial ovarian cancer accounts for about 90% tumor sometime in her life is 6.0-7.0%, of having of ovarian malignancy. They are of three ovarian cancer is almost 1.5% and dying from histological type based on differentiation of ovarian cancer is 1.0%4. There is considerable neoplastic ; serous, mucinous and variability in the incidence & mortality of cancer endometrioid tumors. amongst different racial groups. Blacks are more likely to develop cancer and have higher mortality The main presentation is abdominal distensions than whites, Asians & American Indians, or and pain in abdomen is next common complaint12. Hispanics5. Geographical difference in cancer About 20% of patient have positive family history of

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ovarian cancer13. Ovarian caner is predominantly a MATERIAL AND METHOD disease of postmenopausal age group This study was carried out in Department of (>70yreas); in Pakistan ovarian cancers are seen Pathology, Liaquat University of Medical & Health in early age, where mean age is in between 40- Sciences, Jamshoro from January 2009 to June 4514. 30 % of all ovarian occurring during 2011. Patients diagnosed as ovarian cancer on childhood and adolescence are malignant,15 clinical and radiological grounds were selected. generally originating from germ cell line. One day before surgery we collected 5cc of blood with BD syringe and serum were separated by Although etiology remains unknown, hormonal, centrifuged at 3000 rpm for 10 minutes and environmental and genetic factors play an transfer 500ul serum in aliquots for storage at -20c. important role in the development of ovarian Another sample was collected during first week cancer. In Pakistan various risk factors such as after surgery. early menarche, late menopause, nulliparity, lack of lactation are uncommonly observed16. Younger 100 samples were selected which were age at presentation and higher frequency of morphological proven ovarian cancer & examined positive family history are two unusual features of for CA125, CEA, AFP, & ß-HCG levels for Pakistani patient with ovarian cancer. preoperative and post operative status. They were estimated by solid phase sandwich elecsys Majority of patients had stage III –IV disease at the method by using commercially available kits time of diagnosis, frequency varies 56%-88%16,13,15 (Roche). which is responsible for higher mortality with the disease. Early diagnosis is the only way to Calculations reduced mortality. The analyzer automatically calculates the concentration of each sample in U/ml. For quality Various tumor markers are available which can control we used Elecsys precicontrol tumor help in diagnosis, response of therapy, prognosis marker 1 & 2. and early detection of recurrence. Amongst them cancer antigen (CA-125), Carcinoembryonic RESULTS antigen (CEA), Alpha fetoprotein (AFP), & Beta- A total number of 100 patients with histologically Human chorionic gonadotrophin (ß- HCG) are confirmed malignant ovarian tumors were important and reliable serum biomarkers for early included in this study. The preoperative and detection and prognostification of ovarian postoperative analysis of serum of 100 included cancer17. cases for CA-125, CEA, AFP, & ß-HCG were carried out. Their histological diagnoses were serous CA-125 is the gold standard tumor marker in cystadenocarcinoma (33%), mucinous ovarian cancer. Serum level of CA-125 is used to cystadenocarcinoma (29%), germ cell tumors monitor response to chemotherapy, relapse, & (19%), sex-cord stromal tumors (15%) and other disease progression in ovarian cancer patients18. tumors (4%). Both AFP and ß-HCG play crucial roles in the management of patients with germ cell tumors. CA-125 was seen increased preoperatively in Their levels were elevated in 85 % of patient with 33/33 cases of serous cystadenocarcinoma, 24/29 these tumors19. cases of mucinous cystadenocarcinoma, 10/19 cases of germ cell tumors, 8/15 sex-cord stroma The aim of present study was to evaluate the tumors and negative in Brenner tumor, efficacy of CA-125, CEA, AFP and ß-HCG in , clear cell carcinoma and diagnosis and response to therapy in patient with NHL. While postoperatively, CA-125 level found ovarian cancer. decreased (below the level of 50 IU/ml) in 33/33 of serous cystadenocarcinoma, 23/24 of mucinous

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cystadenocarcinoma, 10/10 germ cell tumor and postoperatively in all except two cases of germ cell 8/8 in sex-cord stromal tumors. These results tumor but below levels of 50 IU/ml which is indicate significant decline of CA-125 in ovarian insignificant for disease (Table-III a & b). cancers following surgical removal / debulking and other treatment. ß-HCG was seen increased preoperatively in 19/19 cases of germ cell tumors and 14/15 cases CEA was seen increased preoperatively only in of sex-cord stromal tumors but seen decreased in mucinous cystadenocarcinoma, which was all cases postoperatively except one case of sex- decreased postoperatively (Table II a & b). cord stromal tumor (Table-IV a & b) which indicate its significance. AFP was seen increased preoperatively in all cases of germ cell tumors, but decreased

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DISCUSSION significance in diagnosis of ovarian cancers. Their This study is an update on subject, which correlate postoperative declines indicate their importance in the histological diagnosis of ovarian tumors with management, prognosis, & recurrence. results of serological tumor marker. Ovarian cancers were one of the most common and most Serum tumor markers CA-125 was important lethal diseases in women throughout the world; its indicators of the epithelial ovarian cancers; similar incidence is even high in developed countries of results reported by Mani R et al. It was more world20. In this study CA-125 is seen more specific specific for serous cystadenocarcinoma. Similar tumor marker for serous cystadenocarcinoma. findings were observed in the study of Mehboob S. CEA is significant in mucinous adenocarcinoma. et al21. The next common group of While AFP and ß-HCG are more important for germ included mucinous tumors; they were also cell and sex-cord stromal tumors, indicate their associated with marked elevations in serum CA-

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125 values, as well as CEA. Similar findings were The next common category of malignant ovarian observed in the study of Mani R et al. tumors comprised of germ cell and sex-cord stromal tumors. These were associated with The value of the tumor marker dropped marked elevation serum of AFP and ß-HCG significantly following appropriate treatment. In markers. Similar findings were reported by Mani R this way it is proved to be having a good et al. The levels of these tumor markers dropped significance in early diagnosis as well as significantly following appropriate treatment. prognostic significance. In this study we have further observed the Combination of CEA, AFP and ß-HCG in malignant increased serum CA-125 level is not only raised in ovarian may give more effective result than using a epithelial ovarian cancers, but also in germ cell & single biomarker. sex cord/stromal tumors.

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CONCLUSIONS SUGGESTION Ovarian malignancy is a serious disease, affecting Patients diagnosed as ovarian malignancies either women of all age group. Majority of the patients as clinical or histological basis are strongly present in advance stage of disease, therefore recommended for serum markers, prognosis is poor and mortality rate is high. Early for diagnosis of bulk of ovarian tumors. These detection and appropriate investigation may help tumor markers may help oncologist / clinicians for to reduce the morbidity and mortality. Clinical, diagnosis, prognosis and treatment of patients. Histological examination and serum ovarian tumor Copyright© 16 May, 2014. marker may help in the diagnosis, prognosis and treatment of ovarian malignancies. REFERENCES 1. Parkin DM, Bray F, Ferley J, Pisani P. Global cancer statistics 2002. CA Cancer J clin 2005; 55; 74-108. 2. Estimating the world cancer burden: Globocan

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