Platinum Resistance in High‐Grade Serous Ovarian Cancer: an Intratumoral Collagen Fiber Implication

Abstract

IntroductionOverall survival of women with high‐grade serous ovarian cancer (HGSOC) is highly related with platinum resistance. Parameters of collagen can be used as potential new prognostic biomarkers, since their relation with tumor growth, invasion and metastasis has been demonstrated. These parameters are (1) quantity which is the amount of fibers deposited, (2) uniformity which refers to how collagen fibers are closely deposited side by side and (3) organization refers to how the fibers are arranged.AimTo evaluate the association of intratumoral collagen fiber parameters with platinum resistance in HGSOC patients.Methods35 women with HGSOC, 14 platinum resistant and 21 platinum sensitive were included. Their samples of paraffin embedded human were sectioned (4 μm) and stained with hematoxylin and eosin. Three intratumoral regions of interest were analyzed by second harmonic generation microscopy, in a Zeiss LSM 780‐NLO confocal (Carl Zeiss AG, Germany). The images were captured (1024×1024 format; 40×/1.3 NA oil) with an excitation wavelength of 890 nm, a pulse length of approximately 100 fs, and emission filter centered at 445 nm with a 20 nm bandwidth (Semrock, Rochester, New York) (Figure 1). Each image was divided in 16 regions (256 × 256) and analyzed in an independently way, using the ImageJ (NIH, Bethesda, USA). Intratumoral collagen fiber parameters were compared considering platinum resistance status using t‐tests. Sensitivity and specificity were analyzed using receiver operator characteristics (ROC) curves.ResultsThere was a significant association between platinum resistance and thick collagen fiber quantity (p=0.04) and a trend of association with thin collagen fiber quantity (p=0.06). Further, intratumoral thick and thin collagen fiber uniformity also were associated with platinum resistance (p=0.02 and p=0.02, respectively). There was no association between intratumoral thick and thin collagen fiber organization with platinum resistance (p=0.29 and p=0.27, respectively). ROC curves demonstrated the highest area under the curve using thin collagen fiber uniformity as parameters, in this case it was found 47.6% of sensibility and 92.9% of specificity to determine platinum resistance (Figure 2).ConclusionOur preliminary results are encouraging since there was an association between intratumoral thick and thin collagen fiber quantity and uniformity with platinum resistance status in women with HGSOC.Support or Funding InformationPartially financed by Cnpq number 306583/2014‐3.