Melanoma: Proia AD

Folberg R, Salomao D, Grossniklaus HE, Proia AD, Rao NA, Cameron JD, Anonymous00355. · Department of Ophthalmology at the University of Illinois at Chicago, 60612, USA. · Hum Pathol. · Pubmed #12612878 No free full text.

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Proia AD. · Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. · J Cutan Pathol. · Pubmed #17944730 No free full text.

Abstract: AIM: Adnexal tumors with divergent lines of differentiation are uncommon. Herein, I report a hamartoma of the eyelid with follicular, sebaceous and apocrine differentiation that exhibited prominent melanin pigmentation. METHODS: A 63-year-old white woman had a nodule present on her left upper eyelid for 15 years. The nodule had been slowly increasing in size but was unchanged in color. Examination disclosed an 8- x 5-mm nodule of the left upper eyelid, with slight purple discoloration. RESULTS: Biopsy showed a well-circumscribed tumor composed of predominantly apocrine glands but with areas of sebaceous and follicular differentiation. Some areas had prominent light-brown, granular pigment within tumor cells. The pigment had histochemical features of neuromelanin. Immunohistochemistry indicated that the hamartomatous elements had antigenic features of various adnexal structures independent of the histological phenotype. The hamartomatous cells did not react with antibodies to tyrosinase or melanoma antigen recognized by T-cells 1 (MART-1). CONCLUSIONS: This case is unique because of its location and prominent melanin pigmentation. Lack of tyrosinase activity in the tumor cells and the periodic acid-Schiff (PAS) positivity of the pigment indicating its similarity to neuromelanin raise the possibility that the melanin in the hamartoma is a non-enzymatically derived oxidation product of a substance intrinsic to the tumor cells.

Rylova SN, Amalfitano A, Persaud-Sawin DA, Guo WX, Chang J, Jansen PJ, Proia AD, Boustany RM. · Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. · Cancer Res. · Pubmed #11830536 links to  free full text

Abstract: Juvenile Batten disease is a neurodegenerative disease caused by accelerated apoptotic death of photoreceptors and neurons attributable to defects in the CLN3 gene. CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor cells. CLN3 negatively modulates endogenous ceramide levels in NT2 cells and acts upstream of ceramide generation. Because defects in regulation of apoptosis are involved in the development of cancer, we evaluated the expression of CLN3 on both mRNA and protein levels in a variety of cancer cell lines and solid colon cancer tissue. We also observed the effect of the blocking of CLN3 protein expression on cancer cell growth, survival, ceramide production, and apoptosis by using an adenovirus-bearing antisense CLN3 construct. We show that CLN3 mRNA and protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma (IMR-32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, SW626, and PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, and HCT 116) cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung (A-549 and NCI-H520) cancer cell lines. CLN3 is also up-regulated in mouse melanoma and breast carcinoma cancer cell lines. We found CLN3 expression is 22-330% higher than in corresponding normal colon control tissue in 8 of 10 solid colon tumors. An adenovirus-expressing antisense CLN3 (Ad-AS-CLN3) blocks CLN3 protein expression in DU-145, BT-20, SW1116, and T98g cancer cell lines as seen by Western blot. Blocking of CLN3 expression using Ad-AS-CLN3 inhibits growth and viability of cancer cells. It also causes elevation in endogenous ceramide production through de novo ceramide synthesis and results in increased apoptosis as shown by propidium iodide and JC-1 staining. This suggests that Ad-AS-CLN3 may be an option for therapy in some cancers. More importantly these results suggest that CLN3 is a novel molecular target for cancer drug discovery.

Butnor KJ, Proia AD. · Department of Pathology, Box 3712, Duke University Medical Center, Durham, NC 27710, USA. · Arch Pathol Lab Med. · Pubmed #11520270 No free full text.

Abstract: BACKGROUND: A full autopsy at our institution includes removal of the eyes for pathologic examination. To our knowledge, the rate of ophthalmic findings at autopsy has not been documented previously. DESIGN: We retrospectively reviewed 277 consecutive autopsies conducted between 1995 and 1999 in which the eyes were removed for examination. Ophthalmic findings were placed in the following categories: I, major findings included those that contributed to the patient's death, would have changed patient management, and/or may have important medical implications for close relatives; II, expected findings after ophthalmologic surgery and minor findings that may have eventually required treatment; and III, incidental findings. RESULTS: Major findings (category I) were found in 32% of autopsies. Minor findings (category II) and incidental findings (category III) were documented in 62% and 34% of autopsies, respectively. Only 14% of autopsies revealed no ophthalmologic diagnoses. CONCLUSION: In our series, postmortem ocular examination revealed a number of important findings, including several heritable and rare conditions. Eighty-six percent of autopsies disclosed at least one pathologic ophthalmologic finding, approximately one third of which demonstrated findings significant enough to have likely required management. Diabetic retinopathy was the most frequent major finding. Malignant melanoma of the choroid was the most commonly found intraocular neoplasm. Chronic uveitis was the most common minor finding. We conclude that important, often unexpected ophthalmic findings are frequently encountered at autopsy, underscoring the relevance of routine postmortem examination of the eyes.