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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 1  |  Page : 54-56
Significance of preoperative thrombocytosis in epithelial ovarian cancer


1 Department of Pathology, St. John's Medical College and Hospital, Sarjapur Road, Bangalore - 560 034, Karnataka, India
2 Department of Gynecologic Oncology, St. John's Medical College and Hospital, Sarjapur Road, Bangalore - 560 034, Karnataka, India
3 Department of Clinical Pathology, St. John's Medical College and Hospital, Sarjapur Road, Bangalore - 560 034, Karnataka, India

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Date of Web Publication19-Jan-2010
 

   Abstract 

Background: Reactive thrombocytosis is reported in a variety of solid tumors. A few studies have documented preoperative thrombocytosis in ovarian cancer and identified it as a marker of aggressive tumor biology.
Aim: To study the incidence of preoperative thrombocytosis (platelets greater than 400x10) in epithelial ovarian cancer and its association with other clinicopathologic factors. Materials and Methods: Sixty-five patients with invasive ovarian epithelial cancer were retrospectively reviewed and analyzed for the association preoperative thrombocytosis with other clinical and histopathological prognostic factors. Means were analyzed by Student's t test; proportions were determined by Chi-square analysis. Results: Twenty of 65 (37.5%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002), more advanced stage disease (P < 0.05) and higher grade tumors (P < 0.02). Patients with thrombocytosis had greater likelihood of subpotimal cytoreduction. Conclusions: Preoperative thrombocytosis is a frequent finding in ovarian carcinomas and their association with advanced stage disease and higher grade denotes that platelets play a role in the tumor growth and progression.

Keywords: Cancer, ovarian cancer, platelets, thrombocytosis

How to cite this article:
Crasta JA, Premlatha T S, Krishnan SM, Vallikad E, Rameshkumar K. Significance of preoperative thrombocytosis in epithelial ovarian cancer. Indian J Pathol Microbiol 2010;53:54-6

How to cite this URL:
Crasta JA, Premlatha T S, Krishnan SM, Vallikad E, Rameshkumar K. Significance of preoperative thrombocytosis in epithelial ovarian cancer. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 Nov 30];53:54-6. Available from: https://www.ijpmonline.org/text.asp?2010/53/1/54/59184



   Introduction Top


Malignancy is one of the most important causes of secondary or reactive thrombocytosis. [1] Platelets and cancer have been associated clinically since the 1800s when the French clinician Armand Trousseau diagnosed himself and several other patients with migratory thrombophlebitis caused by an occult visceral carcinoma. [2] Thrombocytosis (platelet count greater than 400x10 9 ) has been reported in several solid tumors, including lung, renal, gastric, breast, pancreatic and colonic malignancies. [3],[4],[5],[6],[7] In gynecologic malignancies, preoperative elevations in platelet count have been observed in endometrial, vulvar and cervical cancers. [8],[9],[10] In cervical cancer it has been observed that thrombocytosis is a poor prognostic factor in locally advanced node negative disease. [10] A similar association has been observed in advanced epithelial ovarian cancer. [11],[12],[13],[14]

In this study, we report the incidence of thrombocytosis in ovarian carcinoma and attempt to evaluate its association with other clinicopathologic features.


   Materials and Methods Top


The study included 65 women with epithelial ovarian cancer who underwent primary staging exploratory laparotomy for epithelial ovarian cancer at our center. All patients underwent staging laparotomy by a gynecologic oncologist with the intent of optimal cytoreduction. Lymph node dissection was performed wherever technically and medically feasible. Patients received postoperative platinum based chemotherapy and paclitaxel wherever affordable. Patients with tumors of low malignant potential, history of myeloproliferative disorders, acute inflammatory diseases, autoimmune disorders and secondary overt malignancies were excluded from the study. A preoperative complete blood count was available for all the patients.

Patient data was retrospectively retrieved from medical records. The following data was abstracted: preoperative platelet count, hemoglobin, serum CA-125, international federation of gynecology and obstetrics FIGO stage, FIGO grade, histology, optimal or suboptimal cytoreduction, presence of lymph node metastasis. Differences in clinical and histopathologic factors between patients with or without thrombocytosis were examined with the χ2 and student t test. A p value of less than 0.05 was considered statistically significant.


   Results Top


The majority of patients had advanced stage disease at surgery; 50 (76.1%) were found to have stage III/ IV disease whereas 15 had stage I/II disease. International Federation of Gynecology and Obstetrics stage and histologic distribution are given in [Table 1]. Fifteen women had preoperative thrombocytosis (37.5%). The mean platelet count in these women was 610X 10 9 /l (range 410-1210) whereas it was 264X 10 9 /l (range 178-400) in patients without thrombocytosis.

The association between the presence/absence of thrombocytosis and patient clinical and histopathologic parameters are shown in [Table 2]. Thrombocytosis was noted in patients who had greater elevations of CA-125, advanced stage disease and a higher histologic grade, low hemoglobin. There were statistically significant associations observed between the presence of thrombocytosis and hemoglobin, international federation of gynecology and obstetrics FIGO stage and FIGO grade (p < 0.05). There was no association between patient age, histologic type and thrombocytosis status.

All the patients underwent staging laparotomy with the intent of optimal cytoreduction. Tumor cytoreductibility is related to the tumor burden- extent of metastases. Therefore, to study the relationship between thrombocytosis and tumor cytoreducibility we excluded early stage disease and stage IV from further analysis. Optimal cytoreduction was defined as residual disease of less than one cm. Of the 41 stage III patients, 21 had suboptimal cytoreduction whereas 20 had suboptimal cytoreduction and their mean platelet count was 434X10 9 /l and 323X10 9 /l respectively (P < 0.05).


   Discussion Top


Nearly 40% of the patients with inoperable cancers have reactive thrombocytosis. [15] Preoperative thrombocytosis is a frequent finding in ovarian epithelial cancers. When using the standard criteria of thrombocytosis (platelet count of greater than 400x10 9) , the reported incidence varies from 22.4 to 62.5% [11],[12],[13] and 35% in Asian population. [14] The incidence of 37.5% observed in our series is in concordance with the finding in Asian population.

A statistically significant association of thrombocytosis with hemoglobin was observed in our study, which is not reported, in the earlier studies. [11],[12],[13] Reactive thrombocytosis, observed in patients with iron deficiency anemia and hemolytic anemia, may have confounded the results. In our series, the patients with thrombocytosis had lower hemoglobin than the patients without thrombocyosis. Though hemolytic anemia was ruled out serum ferritin levels and bone marrow iron estimation were not performed to rule out thrombocytosis associated with iron deficiency anemia.

Patients with thrombocytosis had higher CA-125 elevations and advanced stage disease which reflect the tumor mass and the tumor burden. A statistically significant association was seen between thrombocytosis and histological grade that reflects the aggressive tumor biology. No association was noted between thrombocytosis and cytoreductibility, as seen in previous studies. [11],[12],[13] This is probably due to the small sample size in our series and due to the large range of platelet counts observed (178-400x10 9 vs.410-1210x10 9 ). Many factors like the extent of disease, skill of the surgeon and the inherent cancer biology influence tumor cytoreductibility. When only stage III group was examined to negate the confounding effects of other factors, the mean platelet count was high in patients who had suboptimal cytoreduction. Since minimal residual disease after cytoreduction is dependent on inherent cancer biology, preoperative thrombocytosis may be a good indicator of suboptimal cytoreduction at exploratory surgery and disease free survival. [11] This is supported by the survival studies in previous series which also showed that patients with thrombocytosis had a significantly shorter overall survival than patients without thrombocytosis (28 months vs. 79 months) in patients with advanced stage disease. [11] It has shown that preoperative thrombocytosis is a poor prognostic indicator in patients with stage III and IVA disease. [11]

Platelets have long been suspected of having a role in cancer progression and metastasis that has been largely attributed to platelet mediated enhancement of tumor cell survival, extravasation and angiogenesis. [2] They are direct sources of tumor cell mitogens stimulating cancer cell proliferation. [2] The possible role of platelets and platelet-derived substances in the metastatic process has been the subject of intense research. Several mechanisms of platelet action in facilitating metastasis have been proposed. Aggregates of circulating cancer cells with platelets may protect against immune-mediated pathways of tumor cell clearance. [16] The platelets, in addition, secrete thrombospondin-1 which facilitates the adhesion of tumor cells to the endothelium, promotes extravasation in the metastatic cascade. [17] The thrombospondin levels have found to be elevated in women with gynecologic malignancies. [18] Once the tumor cells have exited circulation, factors derived from activated platelets are able to induce neoangiogenesis thereby enabling growth at the metastatic site. [19] In addition, platelets secrete a lysophosphaditic acid a bioactive lipid with growth factor like signaling properties as a driving mechanism in bone metastasis by breast and ovarian cancer cells. [20] Interleukin-6 has been associated with ovarian cancer related thrombocytosis. Studies have demonstrated a strong association between ascitic fluid Interleukin-6 levels and circulating platelet counts. [21] Various other hemopoietic factors have been implicated.

Thus the association between thrombocytosis and advanced stage disease and a higher histological grade observed in the present study supports the hypothesis that platelets play a role in tumor growth and progression, thereby reflecting the tumor burden and aggressive tumor biology.

 
   References Top

1.Griesshammer M, Bangerter M, Sauer T, Wennauer R, Bergmann L, Heimpel H. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999;245:295-300.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Gupta GP, Massague J. Platelets and metastasis revisited: a novel fatty link. J Clin Invest 2004;114:1691-3.  Back to cited text no. 2      
3.O'Keefe SC, Marshall FF, Issa MM, Harmon MP, Petros JA. Thrombocytosis is associated with a significant increase in the cancer specific death rate after radical nephrectomy. J Urol 2002;168:1378-80.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Ikeda M, Furukawa H, Imamura H, Shimizu J, Isida H, Masutani S, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol 2002;9:287-91.  Back to cited text no. 4      
5.Benoy I, Salgado R, Colpaert C, Weytjens R, Vermeulen PB, Dirix LY. Serum interleukin 6, plasma VEGF, serum VEGF and VEGF platelet load in breast cancer patients. Clin Breast Cancer 2002;2:311-5.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Schwartz Re, Keny H. Preoperative platelet count predicts survival after resection of periampullary adenocarcinoma. Hepatogastroenterology 2001;48:1493-8.  Back to cited text no. 6      
7.Costantini V, Zacharski LR, Moritz TE, Edwards RL. The platelet counts in lung and colon. Thromb Haemost 1990;64:501-5.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Tamussino KF, Gucer F, Reich O, Moser F, Petru E, Scholz HS. Pretreatment hemoglobin, platelet count and prognosis in endometrial carcinoma. Int J Gynecol Cancer 2001;11:236-40.  Back to cited text no. 8      
9.Hefler L, Mayerhofer K, Leibman B, Obermair A, Reinthraller A, Kainz C, et al. Tumor anemia and thrombocytosisin patients with vulval cancer. Tumor Biol 2000;21:309-14.  Back to cited text no. 9      
10.Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2000;78:137-42.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Li AJ, Madden AC, Cass I, Leuchter RS, Lagasse LD, Karlan BY. The prognostic significance of thrombocytosisin epithelial ovarian carcinoma. Gynecol Oncol 2004;92:211-4.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Zeimet AG, Marth C, Muller Holzner E, Daxenbichler G, Dapunt O. Significance of thrombocytosisin patients with epithelial ovarian cancer. Am J Obstet Gynecol 1994;170:549-54.  Back to cited text no. 12      
13.Menczer J, Schejter E, Geva D, Ginath S, Zakut H. Ovarian carcinoma associated thrombocytosis: correlation with prognostic factors and with survival. Eur J Gynaecol Oncol 1998;12:82-4.  Back to cited text no. 13      
14.Soonthorhthum T, Suraseraneewong V, Kengsakol K, Wijaithum K, Kasemsan P, Prommatt S. Thrombocytosis in advanced epithelial ovarian cancer. J Med Assoc Thai 2007;90:1495-500.  Back to cited text no. 14      
15.Levin J, Conley CL. Thrombocytosis associated with malignant disease. Arch Int Med 1964;114:497-500.  Back to cited text no. 15      
16.Karpatkin S, Pearlstein E. Role of platelets in tumor cell metastasis. Ann Intern Med 1981;95:636-41.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]  
17.Tuszynski GP, Nicosia RF. The role of thrombospondin-1 I tumor progression and angiogenesis. Bioessays 1996;18:71-6.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Natahn FE, Hernandez E, Dunton CJ, Treat J, Swittalska HI, Joseph RR, et al. Plasma thrombospondin levels in patients with gynecologic malignancies. Cancer 1994;73:2853-8.  Back to cited text no. 18      
19.Trikha M, Nakada MT. Platelets and cancer: implications for antiangiogenic therapy. Semin Thromb Hemost 2002;28:39-44.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Boucharaba A Platelet derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 2004;1714-25.  Back to cited text no. 20      
21.Gastl G, Plante M, Finstad CL, Wong GY, Federici MG, Bander NH, et al. High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer. Br J Haematol 1993;83:433-41.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  

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Correspondence Address:
Julian A Crasta
Department of Pathology, St. John's Medical College, Bangalore-560 034, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.59184

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  [Table 1], [Table 2]

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