Diagnosing molecular subtypes of breast cancer by means of Raman spectroscopy.

OBJECTIVES: Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple-negative) from normal tissue in surgical specimens. MATERIALS AND METHODS: Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression. RESULTS: PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple-negative and triple-negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%. CONCLUSION: PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis.

Low prevalence of HPV in Brazilian children with retinoblastoma.

Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,000-30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human ß-globin gene using primers PCO3+/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm.

Low prevalence of HPV in Brazilian children with retinoblastoma

Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,000–30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human β-globin gene using primers PCO3 +/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm

Trilateral retinoblastoma.

BACKGROUND: Trilateral retinoblastoma (TRB) is a syndrome consisting of unilateral or bilateral hereditary retinoblastoma (Rb) associated with an intracranial neuroblastic tumor. Although its incidence is low, the prognosis is very poor. This article reports four cases of TRB and discusses the role of neuroimaging screening for early detection. PROCEDURE: From January 1986 to December 2003, 470 children with Rb were admitted to the Pediatrics and Ophthalmology Departments, A C Camargo Hospital, São Paulo, Brazil. RESULTS: There were four patients with pineoblastoma, two of whom had a positive familial history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at initial diagnosis of Rb. Three patients had bilateral disease and all of them had one eye enucleated, followed by chemotherapy and/or external beam radiation therapy (EBRT). One child with unilateral disease was only submitted to enucleation. In spite of intensive treatment, all patients died with progressive disease within 7, 8, 12, and 12 months after diagnosis of TRB. CONCLUSIONS: Early diagnosis as well as new therapeutic approaches are needed to achieve better results.