Abstract

Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.

Highlights

  • Breast cancer is among the most common cancer in women worldwide and ranks second as a cause of cancer death in women,who are nearly 100 times more likely to develop breast cancer than men [1]

  • Multiphoton microscopy (MPM) Diagnostic Features for Breast Masses Based on multiphoton images obtained, we were able to differentiate normal breast tissues, benign, as well as breast cancer tissues

  • The cyst lining was flattened or absent in some cases. These features were distinctly observed in the multiphoton image and H-E stained image shown in Fig. 3A, B respectively

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Summary

Introduction

Breast cancer is among the most common cancer in women worldwide and ranks second as a cause of cancer death in women,who are nearly 100 times more likely to develop breast cancer than men [1]. Mammography, ultrasound, and other breast imaging methods can help detect a breast abnormality, biopsy followed by pathological analysis is the only definitive way to determine if cancer is present. The routine pathology examination involving fixation, slicing, staining, and being examined under a microscope by pathologists to make a diagnosis, results in a turnaround time ranging from hours to days. This time-consuming technique has the disadvantage of prolonging the surgical procedure and thereby the time the patient stays under general anesthesia, increasing patient morbidity as well as cost of the procedure [2]. It is imperative that a new rapid and label-free noninvasive diagnostic method for breast cancer detection is much needed to reduce the resulting mortality rate

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