Publications (10)36.79 Total impact
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Article: Fitzpatrick skin phototype is an independent predictor of squamous cell carcinoma risk after solid organ transplantation.
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ABSTRACT: BACKGROUND: Solid organ transplant recipients (OTR) are at an increased risk of developing squamous cell carcinoma (SCC) of the skin after transplantation. In predominantly white cohorts, Fitzpatrick skin type (FST) has been reported to be a risk factor for developing posttransplantation skin cancers. OBJECTIVE: Our goal was to determine if FST is a statistically significant risk factor for the development of SCC after solid organ transplantation in a diverse US population of OTR. METHODS: A cohort of OTR completed a questionnaire of demographic factors, transplant type, FST, and skin cancer history. Univariate and multivariate analyses were performed to determine the risk factors for development of SCC after transplantation. RESULTS: As expected, male subjects had an increased risk for SCC compared with female subjects (P = .02), and those aged 50 years and older at the time of transplantation were more likely to develop SCC compared with those younger than 50 years (P < .001). The risk of SCC increased with each incremental decrease in FST, from FST VI to FST I (linear test for trend P < .001). LIMITATIONS: Our questionnaire did not ask specifically about immunosuppressive medications; instead, organ transplant category was used as a proxy for level of immunosuppression. CONCLUSIONS: FST, a patient-reported variable, is an independent risk factor for the development of SCC in OTR, and should be elicited from patients who have gone or will undergo organ transplantation.Journal of the American Academy of Dermatology 10/2012; · 3.99 Impact Factor -
Article: Cutting edge in medical management of cutaneous oncology.
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ABSTRACT: Traditional chemotherapy has resulted in only a modest response, if any, for the 3 most common cutaneous malignancies of basal cell carcinoma, squamous cell carcinoma, and melanoma. Recent advances in understanding of the defects in the pathways driving tumorigenesis have changed the way that we think of these cancers and paved the way to targeted therapy for specific tumors. In this review, we will introduce the novel systemic treatments currently available for these cancers in the context of what is understood about the tumor pathogenesis. We will also introduce ongoing studies that will hopefully broaden our options for highly effective and tolerable treatment.Seminars in cutaneous medicine and surgery 06/2012; 31(2):140-9. · 1.81 Impact Factor -
Article: High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients.
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ABSTRACT: Lung transplant recipients (LTR) have an increased risk of cutaneous squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole, which is associated with phototoxic side effects in some patients, may be an additional risk factor for SCC in this population. To test whether voriconazole is a risk factor for developing SCC in LTR, we evaluated cumulative exposure to voriconazole in 327 adults who underwent lung transplantation at one center between 1991 and 2010. Voriconazole exposure was assessed as a time-varying covariate. We used survival analysis methods to assess the risk of developing SCC over time. Exposure to voriconazole was associated with a 2.6-fold increased risk for SCC. This phenomenon was dose-dependent: the risk for SCC increased by 5.6% with each 60-day exposure at a standard dose of 200 mg twice daily. At 5 years after transplant, voriconazole conferred an absolute risk increase for SCC of 28%. These results suggest that caution should be taken when using voriconazole in LTR because this drug increases the already high risk for SCC in this population.The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2012; 31(7):694-9. · 3.54 Impact Factor -
Article: Validity of patient skin cancer report among organ transplant recipients.
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ABSTRACT: Skin cancer is a common, potentially life-threatening malignancy in organ transplant recipients (OTR), and it is important for transplant physicians to be aware of patient history of skin cancer. Patient self-report represents a quick method of obtaining past medical history of skin cancer but no study has validated the self-report of skin cancer among OTR. Among 339 OTR with a history of skin cancer, the sensitivity and specificity of self-report of non-melanoma skin cancer (NMSC) were 1.00 and 0.92, with a correct classification rate of 0.92. Breakdown of NMSC into squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) resulted in a decrease in correct classification, to 0.83 for SCC and 0.74 for BCC. For SCC, sensitivity was 0.81 and specificity was 0.83, while BCC had a sensitivity of 0.52 and specificity of 0.86. Melanoma self-report had a sensitivity of 0.90 and specificity of 0.86, with a correct classification rate of 0.90. Overall, OTR have comparable accuracy of self-report with the general population. Owing to the high prevalence and increased risk of metastatic potential of skin cancer in this population, the ability to distinguish between cancer types is an important consideration in the dermatologic care of OTR.Clinical Transplantation 03/2012; 26(2):E132-6. · 1.67 Impact Factor -
Article: The 7th edition AJCC staging system for cutaneous squamous cell carcinoma accurately predicts risk of recurrence for heart and lung transplant recipients.
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ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy after solid organ transplantation, with an increased risk of recurrence and metastasis over the general population. The newly updated 7th edition American Joint Committee on Cancer (AJCC) staging system for cSCC is based on consensus expert opinion and requires validation in large cohort studies and in specific patient subpopulations. Our objective was to evaluate the risk of cSCC recurrence in a high-risk population of heart and lung transplant recipients, based on the 7th edition AJCC staging system. We performed a 10-year retrospective cohort study of all primary cSCC diagnosed in heart and lung transplant recipients at a tertiary care academic dermatology center. The cumulative incidence of local recurrence was 4% for cSCC in situ and 19% for stage I cSCC at 5 years, and 54% for stage II cSCC at 3 years. Stage II tumors had a 10-fold greater risk of recurrence than stage I, and a 43-fold greater risk of recurrence than in situ tumors. This study is limited to a specific patient subgroup at a tertiary care center, and may not be generalizable to all populations. Heart and lung transplant recipients are at high risk for local recurrence of cSCC. These data substantiate the prognostic accuracy of the newly updated 7th edition AJCC staging system for stage 0, I, and II cSCC in this population and demonstrate the aggressive behavior of this cancer in immunosuppressed patients.Journal of the American Academy of Dermatology 01/2012; 67(5):829-35. · 3.99 Impact Factor -
Article: Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma
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ABSTRACT: Squamous cell carcinomas (SCCs) are one of the most frequent forms of human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in ∼75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most prevalent tumor suppressor specific to these epithelial malignancies. Notch receptors normally transduce signals in response to ligands on neighboring cells, regulating metazoan lineage selection and developmental patterning. Our findings therefore illustrate a central role for disruption of microenvironmental communication in cancer progression. NOTCH aberrations include frameshift and nonsense mutations leading to receptor truncations as well as point substitutions in key functional domains that abrogate signaling in cell-based assays. Oncogenic gain-of-function mutations in NOTCH1 commonly occur in human T-cell lymphoblastic leukemia/lymphoma and B-cell chronic lymphocytic leukemia. The bifunctional role of Notch in human cancer thus emphasizes the context dependency of signaling outcomes and suggests that targeted inhibition of the Notch pathway may induce squamous epithelial malignancies.Proceedings of the National Academy of Sciences 10/2011; 108(43):17761-17766. · 9.68 Impact Factor -
Article: Temporal dissection of tumorigenesis in primary cancers.
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ABSTRACT: Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.Cancer discovery. 07/2011; 1(2):137-43. -
Article: Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma.
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ABSTRACT: β-Human papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCCs), but no mechanism of carcinogenesis has been determined. We used ultra-high-throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. In all, 67 cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific quantitative PCR. A total of 31 SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18-positive HeLa cervical cancer cell line and HPV16-positive primary cervical and periungual SCCs. Of the tumors, 30% (20/67) were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (P=0.310). Immunosuppression and age were significantly associated with higher viral load (P=0.016 for immunosuppression; P=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV16 and HPV18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCCs.Journal of Investigative Dermatology 04/2011; 131(8):1745-53. · 6.31 Impact Factor -
Article: Catastrophic squamous cell carcinoma in lung transplant patients treated with voriconazole.
Dermatologic Surgery 11/2010; 36(11):1752-5. · 1.80 Impact Factor -
Article: Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole.
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ABSTRACT: Voriconazole is a broad-spectrum antifungal agent associated with photosensitivity and accelerated photoaging. A possible link with aggressive squamous cell carcinoma (SCC) has also been reported. We sought to determine the incidence and frequency of cutaneous SCC among patients undergoing long-term treatment with voriconazole who also manifest features of chronic phototoxicity. We conducted a retrospective review of patients who developed one or more squamous cell neoplasms during long-term treatment with voriconazole at 3 academic dermatology centers. A total of 51 cutaneous SCC were identified in 8 patients (median age 34.5 years, range 9-54) treated with chronic voriconazole (median duration 46.5 months, range 13-60). Underlying diagnoses included graft-versus-host disease, HIV, and Wegener granulomatosis. Signs of chronic phototoxicity and accelerated photoaging included erythema, actinic keratoses, and lentigo formation. The retrospective nature of the study cannot determine the true population risk of SCC associated with voriconazole therapy. A prospective cohort study is needed. A high index of suspicion for photosensitivity and SCC may be warranted with chronic voriconazole use when used in the setting of concurrent immunosuppression.Journal of the American Academy of Dermatology 11/2009; 62(1):31-7. · 3.99 Impact Factor
Top co-authors
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Institutions
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2010–2012
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University of California, San Francisco
- Department of Dermatology
San Francisco, CA, USA
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