Cytologically normal cells from neoplastic cervical samples display extensive structural abnormalities on IR spectroscopy: Implications for tumor biology

Abstract

Fourier-transform IR (FT-IR) spectra of pelleted exfoliated cervical cells from patients with cervical cancer or dysplasia differ from those from normal women. To study the origin of these spectral changes, we obtained the FT-IR spectra of individual cervical cells from normal, dysplastic, and malignant cervical samples. Ninety five percent of normal superficial and intermediate cells displayed two distinct spectral patterns designated A and B, and 5% displayed an intermediate pattern, suggesting extensive structural heterogeneity among these cells. Parabasal and endocervical cells showed pattern B spectra. The spectra of malignant, dysplastic, and other abnormal cells also were characterized. Analysis of FT-IR spectra of over 2,000 individual cells from 10 normal females, 7 females with dysplasia, and 5 females with squamous cell carcinoma revealed that the spectra of normal-appearing intermediate and superficial cells of the cervix from women with either dysplasia or cancer differed from those of normal women. Chemometric and classical spectroscopic analysis showed a continuum of changes paralleling the transition from normalcy to malignancy. These findings suggest that (i) the structural changes underlying the spectroscopic changes are involved in or are a product of cervical carcinogenesis and (ii) the neoplastic process may be more extensive than currently recognized with morphological criteria. This approach may be useful for the structural study of neoplasia and also may be of help in the diagnosis or classification of cervical disorders.Fourier-transform IR spectroscopy (FT-IR) is an emerging method for the study of cancer. We and others have observed that the FT-IR spectra of several human cancers-including colon, skin, and cervical cancer (1-5)-differ from those of their corresponding normal tissues. In cervical cancer, spectral abnormalities have been observed not only in malignant cervical scrapings but also in those with the premalignant condition cervical dysplasia. These findings suggest the occurrence of significant structural, chemical, or metabolic changes associated with cervical carcinogenesis, even at its early stages, and raise the possibility that IR spectroscopy may be useful in the diagnosis of cervical neoplasias.The origin of the spectral changes associated with cervical neoplasia remains unknown. Published studies of exfoliated cervical cells (4-8) have examined pelleted cells, with each spectrum resulting from all cells and extracellular components in the path of the IR beam. Although it appears intuitive that the spectral abnormalities originate in the abnormal cells, proof of this has never been provided. Furthermore, it seems paradoxical that pellets of neoplastic samples (in which the dysplastic or malignant cells are often Ͻ2% of the total) generate grossly abnormal spectra.Resolving these issues requires assessment of the contribution of the individual cellular and noncellular components to the spectra of cervical pellets. To this end, we have developed an approach to o...

Fourier transform infrared (FTIR) spectral mapping of the cervical transformation zone, and dysplastic squamous epithelium

“…Several comprehensive books and articles outline the field [22][23][24][25]. One area that has received considerable attention was the application of the FTIR technique to the diagnosis of cervical neoplasia [26][27][28][29][30][31][32][33][34][35]. Early studies reported spectral differences between exfoliated cells from patients diagnosed normal and dysplastic by cytological [26,27] and histological methods [28,30].…”

Molecular pathology via IR and Raman spectral imaging

“…In spite of these obstacles, work by Cohnford and Rigas [81] relatively early pointed out one of the most relevant aspects of SCP, namely that most cells from an abnormal cervical sample exhibit spectra that are more closely related to the spectral patterns of diagnostic abnormal cells than to those of normal cells. This is true for cells still with normal morphology and therefore, offers the prospects of developing a test with much higher sensitivity than classical cytopathology, since more cells present abnormal properties.…”

The effect of anticancer drugs on seven cell lines monitored by FTIR spectroscopy

“…IR spectroscopy became a powerful tool for cell line identification, biodiagnostics and prognostics. 9,10 In vitro, closely related cancer cells could be distinguished. For instance, the FTIR spectra of various human glioma cell lines were shown to be strongly correlated with their aggressiveness in vivo.…”