Limits...
Macroscopic optical physiological parameters correlate with microscopic proliferation and vessel area breast cancer signatures.

Chung SH, Feldman MD, Martinez D, Kim H, Putt ME, Busch DR, Tchou J, Czerniecki BJ, Schnall MD, Rosen MA, DeMichele A, Yodh AG, Choe R - Breast Cancer Res. (2015)

Bottom Line: The tumor-to-normal relative ratio of Ki67-positive nuclei is positively correlated with DOT-measured relative tissue blood oxygen saturation (R = 0.89, p-value: 0.001), and lower tumor-to-normal deoxy-hemoglobin concentration is associated with higher expression level of Ki67 nuclei (p-value: 0.01).Finally, we find that cell nuclei tend to have more elongated shapes in less oxygenated DOT-measured environments.Overall, the observations corroborate expectations that macroscopic measurements of breast cancer physiology using DOT and DCS can reveal microscopic pathological properties of breast cancer and hold potential to complement pathological biomarker information.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, University of Pennsylvania, 209 S. 33rd St., Philadelphia, PA, 19104, USA. sochung@sas.upenn.edu.

ABSTRACT

Introduction: Non-invasive diffuse optical tomography (DOT) and diffuse correlation spectroscopy (DCS) can detect and characterize breast cancer and predict tumor responses to neoadjuvant chemotherapy, even in patients with radiographically dense breasts. However, the relationship between measured optical parameters and pathological biomarker information needs to be further studied to connect information from optics to traditional clinical cancer biology. Thus we investigate how optically measured physiological parameters in malignant tumors such as oxy-, deoxy-hemoglobin concentration, tissue blood oxygenation, and metabolic rate of oxygen correlate with microscopic histopathological biomarkers from the same malignant tumors, e.g., Ki67 proliferation markers, CD34 stained vasculature markers and nuclear morphology.

Methods: In this pilot study, we investigate correlations of macroscopic physiological parameters of malignant tumors measured by diffuse optical technologies with microscopic histopathological biomarkers of the same tumors, i.e., the Ki67 proliferation marker, the CD34 stained vascular properties marker, and nuclear morphology.

Results: The tumor-to-normal relative ratio of Ki67-positive nuclei is positively correlated with DOT-measured relative tissue blood oxygen saturation (R = 0.89, p-value: 0.001), and lower tumor-to-normal deoxy-hemoglobin concentration is associated with higher expression level of Ki67 nuclei (p-value: 0.01). In a subset of the Ki67-negative group (defined by the 15 % threshold), an inverse correlation between Ki67 expression level and mammary metabolic rate of oxygen was observed (R = -0.95, p-value: 0.014). Further, CD34 stained mean-vessel-area in tumor is positively correlated with tumor-to-normal total-hemoglobin and oxy-hemoglobin concentration. Finally, we find that cell nuclei tend to have more elongated shapes in less oxygenated DOT-measured environments.

Conclusions: Collectively, the pilot data are consistent with the notion that increased blood is supplied to breast cancers, and it also suggests that less conversion of oxy- to deoxy-hemoglobin occurs in more proliferative cancers. Overall, the observations corroborate expectations that macroscopic measurements of breast cancer physiology using DOT and DCS can reveal microscopic pathological properties of breast cancer and hold potential to complement pathological biomarker information.

No MeSH data available.


Related in: MedlinePlus

Correlation between a relative tissue oxygen saturation (rStO2) and rKi67 and b relative oxyhemoglobin concentration (rHbO2) and rKi67 (n = 9). Dotted lines indicate 95 % confidence interval for the mean of the linear fit. These pilot results suggest that more oxygen is present in the more proliferative cancer tissues
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4487833&req=5

Fig3: Correlation between a relative tissue oxygen saturation (rStO2) and rKi67 and b relative oxyhemoglobin concentration (rHbO2) and rKi67 (n = 9). Dotted lines indicate 95 % confidence interval for the mean of the linear fit. These pilot results suggest that more oxygen is present in the more proliferative cancer tissues

Mentions: The percent range of the Ki67-nuclei used for determination of tumor-to-normal ratio of Ki67 (i.e., rKi67) varied from 0.05−23.45 % in cancer tissues (n = 9), and from 0.19−7.41 % in normal tissues (n = 9) (see Additional file 1: Table S2). More subjects were included for the DOT versus cancer-only Ki67-expression comparison study, and the Ki67 range for this latter investigation was 0.05−27.77 % in cancer tissues (n = 18). Among the DOT parameters, rStO2 and rHbO2 were linearly correlated with rKi67 as shown in Fig. 3 and Table 1 (Pearson correlation of 0.89, p-value 0.001 for rStO2, and Pearson correlation of 0.68, p-value 0.044 for rHbO2). Also, for cancer-only Ki67, rHb was inversely correlated with cancer Ki67 percent (Spearman correlation of −0.62, p-value 0.007; see Additional file 1: Table S3 for all correlation values between DOT physiological parameters and cancer Ki67 percent). The range of Ki67 values and those of other molecular biomarkers used in the remainder of the correlation studies are tabulated in Additional file 1: Table S4.Fig. 3


Macroscopic optical physiological parameters correlate with microscopic proliferation and vessel area breast cancer signatures.

Chung SH, Feldman MD, Martinez D, Kim H, Putt ME, Busch DR, Tchou J, Czerniecki BJ, Schnall MD, Rosen MA, DeMichele A, Yodh AG, Choe R - Breast Cancer Res. (2015)

Correlation between a relative tissue oxygen saturation (rStO2) and rKi67 and b relative oxyhemoglobin concentration (rHbO2) and rKi67 (n = 9). Dotted lines indicate 95 % confidence interval for the mean of the linear fit. These pilot results suggest that more oxygen is present in the more proliferative cancer tissues
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487833&req=5

Fig3: Correlation between a relative tissue oxygen saturation (rStO2) and rKi67 and b relative oxyhemoglobin concentration (rHbO2) and rKi67 (n = 9). Dotted lines indicate 95 % confidence interval for the mean of the linear fit. These pilot results suggest that more oxygen is present in the more proliferative cancer tissues
Mentions: The percent range of the Ki67-nuclei used for determination of tumor-to-normal ratio of Ki67 (i.e., rKi67) varied from 0.05−23.45 % in cancer tissues (n = 9), and from 0.19−7.41 % in normal tissues (n = 9) (see Additional file 1: Table S2). More subjects were included for the DOT versus cancer-only Ki67-expression comparison study, and the Ki67 range for this latter investigation was 0.05−27.77 % in cancer tissues (n = 18). Among the DOT parameters, rStO2 and rHbO2 were linearly correlated with rKi67 as shown in Fig. 3 and Table 1 (Pearson correlation of 0.89, p-value 0.001 for rStO2, and Pearson correlation of 0.68, p-value 0.044 for rHbO2). Also, for cancer-only Ki67, rHb was inversely correlated with cancer Ki67 percent (Spearman correlation of −0.62, p-value 0.007; see Additional file 1: Table S3 for all correlation values between DOT physiological parameters and cancer Ki67 percent). The range of Ki67 values and those of other molecular biomarkers used in the remainder of the correlation studies are tabulated in Additional file 1: Table S4.Fig. 3

Bottom Line: The tumor-to-normal relative ratio of Ki67-positive nuclei is positively correlated with DOT-measured relative tissue blood oxygen saturation (R = 0.89, p-value: 0.001), and lower tumor-to-normal deoxy-hemoglobin concentration is associated with higher expression level of Ki67 nuclei (p-value: 0.01).Finally, we find that cell nuclei tend to have more elongated shapes in less oxygenated DOT-measured environments.Overall, the observations corroborate expectations that macroscopic measurements of breast cancer physiology using DOT and DCS can reveal microscopic pathological properties of breast cancer and hold potential to complement pathological biomarker information.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, University of Pennsylvania, 209 S. 33rd St., Philadelphia, PA, 19104, USA. sochung@sas.upenn.edu.

ABSTRACT

Introduction: Non-invasive diffuse optical tomography (DOT) and diffuse correlation spectroscopy (DCS) can detect and characterize breast cancer and predict tumor responses to neoadjuvant chemotherapy, even in patients with radiographically dense breasts. However, the relationship between measured optical parameters and pathological biomarker information needs to be further studied to connect information from optics to traditional clinical cancer biology. Thus we investigate how optically measured physiological parameters in malignant tumors such as oxy-, deoxy-hemoglobin concentration, tissue blood oxygenation, and metabolic rate of oxygen correlate with microscopic histopathological biomarkers from the same malignant tumors, e.g., Ki67 proliferation markers, CD34 stained vasculature markers and nuclear morphology.

Methods: In this pilot study, we investigate correlations of macroscopic physiological parameters of malignant tumors measured by diffuse optical technologies with microscopic histopathological biomarkers of the same tumors, i.e., the Ki67 proliferation marker, the CD34 stained vascular properties marker, and nuclear morphology.

Results: The tumor-to-normal relative ratio of Ki67-positive nuclei is positively correlated with DOT-measured relative tissue blood oxygen saturation (R = 0.89, p-value: 0.001), and lower tumor-to-normal deoxy-hemoglobin concentration is associated with higher expression level of Ki67 nuclei (p-value: 0.01). In a subset of the Ki67-negative group (defined by the 15 % threshold), an inverse correlation between Ki67 expression level and mammary metabolic rate of oxygen was observed (R = -0.95, p-value: 0.014). Further, CD34 stained mean-vessel-area in tumor is positively correlated with tumor-to-normal total-hemoglobin and oxy-hemoglobin concentration. Finally, we find that cell nuclei tend to have more elongated shapes in less oxygenated DOT-measured environments.

Conclusions: Collectively, the pilot data are consistent with the notion that increased blood is supplied to breast cancers, and it also suggests that less conversion of oxy- to deoxy-hemoglobin occurs in more proliferative cancers. Overall, the observations corroborate expectations that macroscopic measurements of breast cancer physiology using DOT and DCS can reveal microscopic pathological properties of breast cancer and hold potential to complement pathological biomarker information.

No MeSH data available.


Related in: MedlinePlus