Tumor Extracellular Hydroxyapatite: A Potential Biomarker For Imaging Ovarian Cancer

Objectives: In ovarian cancer, the criteria to determine whether a patient should undergo primary surgery or be treated with neoadjuvant chemotherapy remain controversial. Furthermore, development of resistance to treatment is common. This is because there are limited biomarkers to predict response to treatment, making the choice of therapy, especially in the recurrent setting, often a matter of trial and error. This may lead to patients being treated with ineffective and toxic therapies. There is clearly a need for more suitable biomarkers that can help predict disease prognosis and which patients may benefit from neoadjuvant chemotherapy versus primary debulking surgery. While tumor calcification has been widely observed in ovarian cancer settings, the origins and significance of these calcifications has never been investigated before. This abstract reports on the discovery of the presence of hydroxyapatite (HAP); Ca10(PO4)6OH2 in the extracellular space of many types of ovarian tumors. We tested 69 annotated tissue microarrays (TMAs) of epithelial ovarian cancer cases patients with ovarian cancer cases originally diagnosed as high-grade serous/papillary ovarian cancer (HGSOC) for HAP. The aim of this investigation was to identify any correlations between tumor extracellular HAP and tumor characteristics, surgical and chemotherapeutic outcome, recurrence and patient survival rate. Methods: The TMAs were stained with alizarin red S for calcium, von Kossa for calcium phosphates, and underwent Raman spectroscopy for calcium phosphate hydroxyapatite. Results: Preliminary analysis of the TMAs showed that 24 cases tested positive for extracellular HAP (see figure 1 for example). Within these 28 HAP positive cases, 83% were HGSOC, the overall survival was 2.63 ± 1.97 years (mean ± STD) post diagnosis and 38% of cases had recurrence post treatment. On the other hand, of those cases that were negative for extracellular HAP, only 41% were HGSOC, the overall survival was 3.80 ± 3.69 years, and only 20% of those cases had tumor recurrence. Conclusions: Those the sample size tested was small and no statistical significance could be established, the results demonstrate the potential importance for testing patients with ovarian tumors for extracellular HAP. Additionally, the lower overall survival and higher recurrence rates of the cases with HAP compared to those without may suggest that not only should patients with ovarian tumors that contain extracellular HAP be monitored more frequently post treatment, but also a different treatment approach altogether may be merited. In ovarian cancer, the criteria to determine whether a patient should undergo primary surgery or be treated with neoadjuvant chemotherapy remain controversial. Furthermore, development of resistance to treatment is common. This is because there are limited biomarkers to predict response to treatment, making the choice of therapy, especially in the recurrent setting, often a matter of trial and error. This may lead to patients being treated with ineffective and toxic therapies. There is clearly a need for more suitable biomarkers that can help predict disease prognosis and which patients may benefit from neoadjuvant chemotherapy versus primary debulking surgery. While tumor calcification has been widely observed in ovarian cancer settings, the origins and significance of these calcifications has never been investigated before. This abstract reports on the discovery of the presence of hydroxyapatite (HAP); Ca10(PO4)6OH2 in the extracellular space of many types of ovarian tumors. We tested 69 annotated tissue microarrays (TMAs) of epithelial ovarian cancer cases patients with ovarian cancer cases originally diagnosed as high-grade serous/papillary ovarian cancer (HGSOC) for HAP. The aim of this investigation was to identify any correlations between tumor extracellular HAP and tumor characteristics, surgical and chemotherapeutic outcome, recurrence and patient survival rate. The TMAs were stained with alizarin red S for calcium, von Kossa for calcium phosphates, and underwent Raman spectroscopy for calcium phosphate hydroxyapatite. Preliminary analysis of the TMAs showed that 24 cases tested positive for extracellular HAP (see figure 1 for example). Within these 28 HAP positive cases, 83% were HGSOC, the overall survival was 2.63 ± 1.97 years (mean ± STD) post diagnosis and 38% of cases had recurrence post treatment. On the other hand, of those cases that were negative for extracellular HAP, only 41% were HGSOC, the overall survival was 3.80 ± 3.69 years, and only 20% of those cases had tumor recurrence. Those the sample size tested was small and no statistical significance could be established, the results demonstrate the potential importance for testing patients with ovarian tumors for extracellular HAP. Additionally, the lower overall survival and higher recurrence rates of the cases with HAP compared to those without may suggest that not only should patients with ovarian tumors that contain extracellular HAP be monitored more frequently post treatment, but also a different treatment approach altogether may be merited.