Hybrid Spectral-IRDx: Near-IR and Ultrasound Attenuation System for Differentiating Breast Cancer From Adjacent Normal Tissue.

OBJECTIVE: While performing surgical excision for breast cancer (lumpectomy), it is important to ensure a clear margin of normal tissue around the cancer to achieve complete resection. The current standard is histopathology; however, it is time-consuming and labour-intensive requiring skilled personnel. METHOD: We describe a Hybrid Spectral-IRDx - a combination of the previously reported Spectral-IRDx tool with multimodal ultrasound and NIR spectroscopy techniques. We show how this portable, cost-effective, minimal-contact tool could provide rapid diagnosis of cancer using formalin-fixed (FF) and deparaffinized (DP) breast biopsy tissues. RESULTS: Using this new tool, measurements were performed on cancerous/fibroadenoma and its adjacent normal tissues from the same patients (N = 14). The acoustic attenuation coefficient (α) and reduced scattering coefficient (µ's) (at 850, 940, and 1060 nm) for the cancerous/fibroadenoma tissues were reported to be higher compared to adjacent normal tissues, a basis of delineation. Comparing FF cancerous and adjacent normal tissue, the difference in µ's at 850 nm and 940 nm were statistically significant (p = 3.17e-2 and 7.94e-3 respectively). The difference in α between the cancerous and adjacent normal tissues for DP and FF tissues were also statistically significant (p = 2.85e-2 and 7.94e-3 respectively). Combining multimodal parameters α and µ's (at 940 nm) show highest statistical significance (p = 6.72e-4) between FF cancerous/fibroadenoma and adjacent normal tissues. CONCLUSION: We show that Hybrid Spectral-IRDx can accurately delineate between cancerous and adjacent normal breast biopsy tissue. SIGNIFICANCE: The results obtained establish the proof-of-principle and large-scale testing of this multimodal breast cancer diagnostic platform for core biopsy diagnosis.

High expression of integrin ß6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.

Integrin αvß6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin ß6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvß6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin ß6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvß6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.

Pediatric tumors of the central nervous system: a retrospective study of 1,043 cases from a tertiary care center in South India.

OBJECTIVE: The objective of this study is to describe the age, sex, location, and histopathology of pediatric tumors of the central nervous system diagnosed at a tertiary care center in South India. PATIENTS AND METHODS: One thousand forty-three tumors that occurred in children between 0 and 18 years of age diagnosed between 1 January 1990 and 31 December 2004 were reclassified according to the WHO 2007 classification, and the clinical data were analyzed. RESULTS: The mean age at diagnosis was 10.9 years with a male/female ratio of 1.7:1 with a male preponderance in most tumors. The five most frequent tumors were: astrocytoma (47.3%), medulloblastoma (11.4%), craniopharyngioma (9.7%), ependymal tumors (4.8%), and nerve sheath tumors (4.1%). Of these, 53.3% of the tumors were supratentorial, 40.6% were infratentorial, and 6.1% occurred in the spinal cord. Although the number of patients treated annually steadily increased over the study period, there was no relative increase in pediatric neoplasms compared to adults. CONCLUSIONS: The majority of tumors showed a male preponderance with astrocytoma being the most common tumor type. Although the cerebellum was the most frequent single site of occurrence, tumors involved the supraratentorial compartment more often than the infratentorial compartment.