Optical biomarkers of serous and mucinous human ovarian tumor assessed with nonlinear optics microscopies.
BACKGROUND
Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression.


RESULTS
We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells.


CONCLUSIONS
NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions.
Biophotonic Group, Optics and Photonics Research Center (CEPOF), Institute of Physics Gleb Wataghin, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil. jadur@bioingenieria.edu.ar
Javier
J
Adur
Vitor B
VB
Pelegati
Andre A
AA
de Thomaz
Mariana O
MO
Baratti
Diogo B
DB
Almeida
L A L A
LA
Andrade
Fátima
F
Bottcher-Luiz
Hernandes F
HF
Carvalho
Carlos L
CL
Cesar
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008853:Microscopy; D036641:Microscopy, Fluorescence, Multiphoton; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D044967:Serum / Q000378:metabolism*
D014408:Biomarkers, Tumor