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nalling promotes the presentation of antigenic TIF1c and leads to the emergence of anti-TIF1c autoantibodies in malignancyassociated TIF1c+ dermatomyositis. A. Kasuya,* T. Hoshino, M. Aoshima, K. Tatsuno, T. Fujiyama, Y. Tokura
tolerance induced by transforming growth factor-beta2-treated antigenpresenting cells. Immunology 2008; 124: 304–314. 9 Kobie JJ, Wu RS, Kurt RA et al. Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 2003; 63: 1860–1864. DOI: 10.1111/jdv.12569
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan *Correspondence: A. Kasuya. E-mail: [email protected]
References 1 Fujimoto M, Hamaguchi Y, Kaji K et al. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 2012; 64: 513–522. 2 Kasuya A, Hamaguchi Y, Fujimoto M, Tokura Y. TIF1gamma-overexpressing, highly progressive endometrial carcinoma in a patient with dermato-myositis positive for malignancy-associated anti-p155/140 autoantibody. Acta Derm Venereol 2013; 93: 715–716. 3 Andrieux G, Fattet L, Le Borgne M, Rimokh R, Theret N. Dynamic regulation of Tgf-B signaling by Tif1gamma: a computational approach. PLoS ONE 2012; 7: e33761. 4 Beswick EJ, Pinchuk IV, Earley RB, Schmitt DA, Reyes VE. Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4 + T cell proliferation and development of regulatory T cells during Helicobacter pylori infection. Infect Immun 2011; 79: 2737–2745. 5 Wahl SM, Hunt DA, Wong HL et al. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol 1988; 140: 3026–3032. 6 Inman GJ. Switching TGFbeta from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev 2011; 21: 93–99. 7 Fleming NI, Jorissen RN, Mouradov D et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res 2013; 73: 725–735. 8 Zhang H, Yang P, Zhou H, Meng Q, Huang X. Involvement of Foxp3expressing CD4+ CD25+ regulatory T cells in the development of
(a)
Warty intralymphatic histiocytosis successfully treated with topical tacrolimus Editor Intralymphatic histiocytosis (ILH) is an extremely rare benign condition first described in 1994 by O’Grady et al.1 The characteristic histological feature is the intraluminal aggregation of histiocytes in the dermis. In 2009, Requena et al.2 reported 16 cases of ILH. Including these, only 54 cases of ILH have been reported to date,2–8 and there has been no established treatment. Herein, we describe a novel clinical type of verrucous ILH at a surgical site of synovectomy successfully treated with topical tacrolimus ointment. A 49-year-old female presented with an asymptomatic, hyperkeratotic, 20-mm-diameter dome-shaped tumour on the dorsum of her right wrist (Fig. 1a). She had been treated with oral methotrexate for rheumatoid arthritis at 4–16 mg/week for 4 years. One year prior to her referral to our hospital, she had undergone synovectomy of the right wrist at another
(b)
(c) Figure 1 (a) The lesion before total excision presents as a hyperkeratotic tumour of 20 mm in diameter on the right wrist. (b) The site at 61 days after total excision. A recurrent lesion is seen. (c) A photo at 30 days after the start of twicedaily 0.1% tacrolimus ointment. The recurrent lesion has largely disappeared.
JEADV 2015, 29, 2255–2273
© 2014 European Academy of Dermatology and Venereology
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(a)
(c)
(b)
(d)
orthopaedic clinic. No foreign material was implanted during her surgery. The tumour had gradually developed at the surgical site during the 8 months before the patient came to us on referral. We performed removal of the entire tumour, and the lesion was found to be histopathologically exophytic and papillomatous (Fig. 2a). The rete ridges were elongated, and koilocytotic cells were observed. In the dermis, fibroblastic-cell proliferation and patchy inflammatory-cell infiltration were seen. In addition, dilated thin-walled vascular channels were seen in the dermis, many of them containing aggregates of histiocytic cells (Fig. 2b). These cells were positive for CD68 (Fig. 2c). The endothelial cells lining the dilated lumina were positive for D2-40, which confirmed their lymphatic vessel nature (Fig. 2d). We performed polariscopic examination and no foreign material was detected. On the basis of these findings, we made the final diagnosis of verrucous ILH. Clinically, we dermatologists recognize ILH as irregular erythematous plaques with or without a livedo-like eruptions, papules, vesicles or nodules.9 The clinical and pathological features of verruca vulgaris-like epidermis have not been previously described before. With respect to the koilocytes in the epidermis, we investigated the subtype of human papillomavirus (HPV) by PCR; however, no subtype of HPV was amplified. We performed full-thickness skin graft towards the defect, and we have been following her up carefully on an outpatient basis. Two months after the removal, a recurrent lesion appeared on the skin graft (Fig. 1b). We performed the skin biopsy and proved the recurrence of ILH. We prescribed 0.1% tacrolimus ointment applied topically twice a day, and the lesion disappeared after 1 month (Fig. 1c).
JEADV 2015, 29, 2255–2273
Figure 2 Histopathology of the lesion. (a) Histopathology of the surgical specimen. The epidermis resembles verrucous vulgaris. (Haematoxylin and eosin; original magnification 940). (b) Dilated vascular channels are seen in the dermis, many of them containing aggregates of mononuclear histiocytes. (Haematoxylin and eosin; original magnification 9100). (c) These cells were positive for CD68. (d) The endothelial cells of dilated vessels were positive for D2-40.
ILH is a rare benign cutaneous condition that is mainly characterized by the complication of long-lasting rheumatoid arthritis and the histological presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes in their lumina. ILH usually represents a benign process with a chronic and indolent course; however, recurrence is very common regardless of the therapeutic intervention. There have been no specific or consistent treatments in the past, and no evidencebased consensus guidelines exist. In this case, we first performed complete excision of the lesion, but it soon recurred. We tried topical 0.1% tacrolimus ointment twice a day, and the lesion disappeared immediately. We saw no adverse effects during this period. In conclusion, this is the first report to show the therapeutic effectiveness of topical 0.1% tacrolimus ointment against ILH without any side-effects. The precise mechanism of action is unclear at present. However, we may consider topical 0.1% tacrolimus ointment as one of the therapeutic measures. M. Tsujiwaki, H. Hata,* T. Miyauchi, E. Homma, S. Aoyagi, H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan *Correspondence: H. Hata. E-mail: [email protected]
References 1 O’Grady JT, Shahidullah H, Doherty VR, al-Naffussi A. Intravascular histiocytosis. Histopathology 1994; 24: 265–268. 2 Requena L, El-Shabrawi-Caelen L, Walsh SN et al. Intralymphatic histiocytosis. a clinicopathologic study of 16 cases. Am J Dermatopathol 2009; 31: 140–151.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
3 Bakr F, Webber N, Fassihi H et al. Primary and secondary intralymphatic histiocytosis. J Am Acad Dermatol 2014; 70: 927–933. 4 Korman JB, Burgin S, Tahan SR. Intralymphatic histiocytosis in association with severe osteoarthritis of the shoulder. J Am Acad Dermatol 2013; 69: e314–e315. 5 Washio K, Nakata K, Nakamura A, Horikawa T. Pressure bandage as an effective treatment for intralymphatic histiocytosis associated with rheumatoid arthritis. Dermatology 2011; 223: 20–24. 6 Saggar S, Lee B, Krivo J, Jacobson M, Krishnamurthy K. Intralymphatic histiocytosis associated with orthopedic implants. J Drugs Dermatol 2011; 10: 1208–1209. 7 Wang Y, Yang H, Tu P. Upper facial swelling: an uncommon manifestation of intralymphatic histiocytosis. Eur J Dermatol 2012; 22: 814–815. 8 de Unamuno Bustos B, Garcia Rabasco A, Ballester Sanchez R, Martinez Aparicio A, Alegre de Miquel V. Erythematous indurated plaque on the right upper limb. Intralymphatic histiocytosis (IH) associated with orthopedic metal implant. Int J Dermatol 2013; 52: 547–549. 9 Sakaguchi M, Nagai H, Tsuji G, Morinobu A, Kumagai S, Nishigori C. Effectiveness of infliximab for intralymphatic histiocytosis with rheumatoid arthritis. Arch Dermatol 2011; 147: 131–133. DOI: 10.1111/jdv.12570
Early changes in miRNA expression are predictive of response to extracorporeal photopheresis in cutaneous T-cell lymphoma Editor Mycosis fungoides (MF) and Sezary syndrome (SS), major variants of cutaneous T-cell lymphoma (CTCL), are malignancies of clonal T lymphocytes, and advanced MF/SS are associated with a 40–47% 5-year survival.1–4 Extracorporeal photopheresis (ECP), a therapy for CTCL, has been demonstrated to have a mean time to clinical response of 22.4 9.6 weeks, which indicates patients should be treated with ECP for up to 8 months before effectiveness can be accurately assessed.5 Currently, we cannot predict who will respond to ECP. MicroRNA (miRNA) are small, non-coding RNA that can inhibit protein translation.6 CTCL has been reported to have altered miRNA expression, including reduced miR-191, miR-223, miR342, and increased miR-155.7–9 The primary goal of this study was to determine if a select miRNA profile in peripheral blood mononuclear cells (PBMC) obtained at baseline and 3 months of ECP monotherapy could predict clinical response to ECP. This retrospective study utilized the CTCL tissue repository at Johns Hopkins and was approved by the Johns Hopkins Institutional Review Board. Thirteen subjects were selected with biopsy-proven MF or SS and use of monotherapy ECP. A single
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Dermatologist oversaw the administration of and response to ECP, as described previously.10 Immediately before the start of ECP and 3 months later, blood was taken and PBMC were isolated and cryopreserved in liquid nitrogen. Total RNA was extracted and TaqMan miRNA Assays were run in triplicate, and expression was compared with RNU24. The Student’s t-test and Fisher’s exact test were used to evaluate for significant differences. Of the 13 subjects, five (38%) achieved an overall clinical response (minimal and partial responses; MR/PR) at the final evaluation (12-month ECP monotherapy or at addition of new systemic therapy). Evaluation of the fold change in miR-223 from baseline to 3 months post-ECP therapy identified a significant increase in miR-223 in those who had a final response (n = 5) vs. those with no response or disease progression (NR/ DP; n = 8) [3.56 (SEM 1.19) vs. 0.75 (SEM 0.15) *P = 0.01; Fig. 1a,b]. Those whose miR-223 increased over 1.5-fold from baseline to 3 months were more likely to respond to ECP (**P < 0.01; Fig. 1c). We also identified an increase in the mean fold change of both miR-191 and miR-342 in MR/PR (n = 3) vs. NR/DP (n = 6) after 3 months of ECP treatment [miR-191: 1.59 (SEM 0.39) vs. 0.86 (SEM 0.13) * P = 0.05; miR-342: 1.68 (SEM 0.29) vs. 0.91 (SEM 0.16) ** P = 0.04; Fig. 2a,b]. We did not identify a significant difference in 3-month change of miR-423-5p (expression not altered in CTCL)8 or miR155, and there was no difference in baseline expression of any miRNA between responders and non-responders. We demonstrate that an early increase of PBMC miR-191, miR-223 and miR-342 at 3 months post therapy is predictive of a clinical response to ECP between 6 and 12 months. It is not clear if ECP directly increases levels of these miRNA in the malignant T cell, or if the increase is due to an influx of normal PBMC. Measurement of these miRNA levels is nonetheless useful to help predict those who will respond to ECP. Notably, the miR-423-5p and miR-155 expression did not differ, indicating that our results represent a selective upregulation and not a global miRNA increase. In advanced MF/SS, we are encountering a dire clinical scenario, as patients face high mortality, limited therapeutic options and often a long median time to response with current therapies. Therefore, it is imperative we identify predictors of response for ECP to reduce time spent on futile therapies with an overall goal of enhancing patient survival. Larger studies are warranted to further evaluate the role of miRNA as predictors of response to therapy in MF/SS.
Funding sources L.Y.M. is supported by the Dermatology Foundation, and NIH/ NCI (K12CA090625), American Cancer Society (IRG-58-00951), NIH (UL1TR000445), and the Vanderbilt Department of Medicine/Dermatology. C.M.E. is supported by R01CA148950 and the Vanderbilt Department of Pathology, Microbiology and Immunology.
© 2014 European Academy of Dermatology and Venereology
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nalling promotes the presentation of antigenic TIF1c and leads to the emergence of anti-TIF1c autoantibodies in malignancyassociated TIF1c+ dermatomyositis. A. Kasuya,* T. Hoshino, M. Aoshima, K. Tatsuno, T. Fujiyama, Y. Tokura
tolerance induced by transforming growth factor-beta2-treated antigenpresenting cells. Immunology 2008; 124: 304–314. 9 Kobie JJ, Wu RS, Kurt RA et al. Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 2003; 63: 1860–1864. DOI: 10.1111/jdv.12569
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan *Correspondence: A. Kasuya. E-mail: [email protected]
References 1 Fujimoto M, Hamaguchi Y, Kaji K et al. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 2012; 64: 513–522. 2 Kasuya A, Hamaguchi Y, Fujimoto M, Tokura Y. TIF1gamma-overexpressing, highly progressive endometrial carcinoma in a patient with dermato-myositis positive for malignancy-associated anti-p155/140 autoantibody. Acta Derm Venereol 2013; 93: 715–716. 3 Andrieux G, Fattet L, Le Borgne M, Rimokh R, Theret N. Dynamic regulation of Tgf-B signaling by Tif1gamma: a computational approach. PLoS ONE 2012; 7: e33761. 4 Beswick EJ, Pinchuk IV, Earley RB, Schmitt DA, Reyes VE. Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4 + T cell proliferation and development of regulatory T cells during Helicobacter pylori infection. Infect Immun 2011; 79: 2737–2745. 5 Wahl SM, Hunt DA, Wong HL et al. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol 1988; 140: 3026–3032. 6 Inman GJ. Switching TGFbeta from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev 2011; 21: 93–99. 7 Fleming NI, Jorissen RN, Mouradov D et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res 2013; 73: 725–735. 8 Zhang H, Yang P, Zhou H, Meng Q, Huang X. Involvement of Foxp3expressing CD4+ CD25+ regulatory T cells in the development of
(a)
Warty intralymphatic histiocytosis successfully treated with topical tacrolimus Editor Intralymphatic histiocytosis (ILH) is an extremely rare benign condition first described in 1994 by O’Grady et al.1 The characteristic histological feature is the intraluminal aggregation of histiocytes in the dermis. In 2009, Requena et al.2 reported 16 cases of ILH. Including these, only 54 cases of ILH have been reported to date,2–8 and there has been no established treatment. Herein, we describe a novel clinical type of verrucous ILH at a surgical site of synovectomy successfully treated with topical tacrolimus ointment. A 49-year-old female presented with an asymptomatic, hyperkeratotic, 20-mm-diameter dome-shaped tumour on the dorsum of her right wrist (Fig. 1a). She had been treated with oral methotrexate for rheumatoid arthritis at 4–16 mg/week for 4 years. One year prior to her referral to our hospital, she had undergone synovectomy of the right wrist at another
(b)
(c) Figure 1 (a) The lesion before total excision presents as a hyperkeratotic tumour of 20 mm in diameter on the right wrist. (b) The site at 61 days after total excision. A recurrent lesion is seen. (c) A photo at 30 days after the start of twicedaily 0.1% tacrolimus ointment. The recurrent lesion has largely disappeared.
JEADV 2015, 29, 2255–2273
© 2014 European Academy of Dermatology and Venereology
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(a)
(c)
(b)
(d)
orthopaedic clinic. No foreign material was implanted during her surgery. The tumour had gradually developed at the surgical site during the 8 months before the patient came to us on referral. We performed removal of the entire tumour, and the lesion was found to be histopathologically exophytic and papillomatous (Fig. 2a). The rete ridges were elongated, and koilocytotic cells were observed. In the dermis, fibroblastic-cell proliferation and patchy inflammatory-cell infiltration were seen. In addition, dilated thin-walled vascular channels were seen in the dermis, many of them containing aggregates of histiocytic cells (Fig. 2b). These cells were positive for CD68 (Fig. 2c). The endothelial cells lining the dilated lumina were positive for D2-40, which confirmed their lymphatic vessel nature (Fig. 2d). We performed polariscopic examination and no foreign material was detected. On the basis of these findings, we made the final diagnosis of verrucous ILH. Clinically, we dermatologists recognize ILH as irregular erythematous plaques with or without a livedo-like eruptions, papules, vesicles or nodules.9 The clinical and pathological features of verruca vulgaris-like epidermis have not been previously described before. With respect to the koilocytes in the epidermis, we investigated the subtype of human papillomavirus (HPV) by PCR; however, no subtype of HPV was amplified. We performed full-thickness skin graft towards the defect, and we have been following her up carefully on an outpatient basis. Two months after the removal, a recurrent lesion appeared on the skin graft (Fig. 1b). We performed the skin biopsy and proved the recurrence of ILH. We prescribed 0.1% tacrolimus ointment applied topically twice a day, and the lesion disappeared after 1 month (Fig. 1c).
JEADV 2015, 29, 2255–2273
Figure 2 Histopathology of the lesion. (a) Histopathology of the surgical specimen. The epidermis resembles verrucous vulgaris. (Haematoxylin and eosin; original magnification 940). (b) Dilated vascular channels are seen in the dermis, many of them containing aggregates of mononuclear histiocytes. (Haematoxylin and eosin; original magnification 9100). (c) These cells were positive for CD68. (d) The endothelial cells of dilated vessels were positive for D2-40.
ILH is a rare benign cutaneous condition that is mainly characterized by the complication of long-lasting rheumatoid arthritis and the histological presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes in their lumina. ILH usually represents a benign process with a chronic and indolent course; however, recurrence is very common regardless of the therapeutic intervention. There have been no specific or consistent treatments in the past, and no evidencebased consensus guidelines exist. In this case, we first performed complete excision of the lesion, but it soon recurred. We tried topical 0.1% tacrolimus ointment twice a day, and the lesion disappeared immediately. We saw no adverse effects during this period. In conclusion, this is the first report to show the therapeutic effectiveness of topical 0.1% tacrolimus ointment against ILH without any side-effects. The precise mechanism of action is unclear at present. However, we may consider topical 0.1% tacrolimus ointment as one of the therapeutic measures. M. Tsujiwaki, H. Hata,* T. Miyauchi, E. Homma, S. Aoyagi, H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan *Correspondence: H. Hata. E-mail: [email protected]
References 1 O’Grady JT, Shahidullah H, Doherty VR, al-Naffussi A. Intravascular histiocytosis. Histopathology 1994; 24: 265–268. 2 Requena L, El-Shabrawi-Caelen L, Walsh SN et al. Intralymphatic histiocytosis. a clinicopathologic study of 16 cases. Am J Dermatopathol 2009; 31: 140–151.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
3 Bakr F, Webber N, Fassihi H et al. Primary and secondary intralymphatic histiocytosis. J Am Acad Dermatol 2014; 70: 927–933. 4 Korman JB, Burgin S, Tahan SR. Intralymphatic histiocytosis in association with severe osteoarthritis of the shoulder. J Am Acad Dermatol 2013; 69: e314–e315. 5 Washio K, Nakata K, Nakamura A, Horikawa T. Pressure bandage as an effective treatment for intralymphatic histiocytosis associated with rheumatoid arthritis. Dermatology 2011; 223: 20–24. 6 Saggar S, Lee B, Krivo J, Jacobson M, Krishnamurthy K. Intralymphatic histiocytosis associated with orthopedic implants. J Drugs Dermatol 2011; 10: 1208–1209. 7 Wang Y, Yang H, Tu P. Upper facial swelling: an uncommon manifestation of intralymphatic histiocytosis. Eur J Dermatol 2012; 22: 814–815. 8 de Unamuno Bustos B, Garcia Rabasco A, Ballester Sanchez R, Martinez Aparicio A, Alegre de Miquel V. Erythematous indurated plaque on the right upper limb. Intralymphatic histiocytosis (IH) associated with orthopedic metal implant. Int J Dermatol 2013; 52: 547–549. 9 Sakaguchi M, Nagai H, Tsuji G, Morinobu A, Kumagai S, Nishigori C. Effectiveness of infliximab for intralymphatic histiocytosis with rheumatoid arthritis. Arch Dermatol 2011; 147: 131–133. DOI: 10.1111/jdv.12570
Early changes in miRNA expression are predictive of response to extracorporeal photopheresis in cutaneous T-cell lymphoma Editor Mycosis fungoides (MF) and Sezary syndrome (SS), major variants of cutaneous T-cell lymphoma (CTCL), are malignancies of clonal T lymphocytes, and advanced MF/SS are associated with a 40–47% 5-year survival.1–4 Extracorporeal photopheresis (ECP), a therapy for CTCL, has been demonstrated to have a mean time to clinical response of 22.4 9.6 weeks, which indicates patients should be treated with ECP for up to 8 months before effectiveness can be accurately assessed.5 Currently, we cannot predict who will respond to ECP. MicroRNA (miRNA) are small, non-coding RNA that can inhibit protein translation.6 CTCL has been reported to have altered miRNA expression, including reduced miR-191, miR-223, miR342, and increased miR-155.7–9 The primary goal of this study was to determine if a select miRNA profile in peripheral blood mononuclear cells (PBMC) obtained at baseline and 3 months of ECP monotherapy could predict clinical response to ECP. This retrospective study utilized the CTCL tissue repository at Johns Hopkins and was approved by the Johns Hopkins Institutional Review Board. Thirteen subjects were selected with biopsy-proven MF or SS and use of monotherapy ECP. A single
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2269
Dermatologist oversaw the administration of and response to ECP, as described previously.10 Immediately before the start of ECP and 3 months later, blood was taken and PBMC were isolated and cryopreserved in liquid nitrogen. Total RNA was extracted and TaqMan miRNA Assays were run in triplicate, and expression was compared with RNU24. The Student’s t-test and Fisher’s exact test were used to evaluate for significant differences. Of the 13 subjects, five (38%) achieved an overall clinical response (minimal and partial responses; MR/PR) at the final evaluation (12-month ECP monotherapy or at addition of new systemic therapy). Evaluation of the fold change in miR-223 from baseline to 3 months post-ECP therapy identified a significant increase in miR-223 in those who had a final response (n = 5) vs. those with no response or disease progression (NR/ DP; n = 8) [3.56 (SEM 1.19) vs. 0.75 (SEM 0.15) *P = 0.01; Fig. 1a,b]. Those whose miR-223 increased over 1.5-fold from baseline to 3 months were more likely to respond to ECP (**P < 0.01; Fig. 1c). We also identified an increase in the mean fold change of both miR-191 and miR-342 in MR/PR (n = 3) vs. NR/DP (n = 6) after 3 months of ECP treatment [miR-191: 1.59 (SEM 0.39) vs. 0.86 (SEM 0.13) * P = 0.05; miR-342: 1.68 (SEM 0.29) vs. 0.91 (SEM 0.16) ** P = 0.04; Fig. 2a,b]. We did not identify a significant difference in 3-month change of miR-423-5p (expression not altered in CTCL)8 or miR155, and there was no difference in baseline expression of any miRNA between responders and non-responders. We demonstrate that an early increase of PBMC miR-191, miR-223 and miR-342 at 3 months post therapy is predictive of a clinical response to ECP between 6 and 12 months. It is not clear if ECP directly increases levels of these miRNA in the malignant T cell, or if the increase is due to an influx of normal PBMC. Measurement of these miRNA levels is nonetheless useful to help predict those who will respond to ECP. Notably, the miR-423-5p and miR-155 expression did not differ, indicating that our results represent a selective upregulation and not a global miRNA increase. In advanced MF/SS, we are encountering a dire clinical scenario, as patients face high mortality, limited therapeutic options and often a long median time to response with current therapies. Therefore, it is imperative we identify predictors of response for ECP to reduce time spent on futile therapies with an overall goal of enhancing patient survival. Larger studies are warranted to further evaluate the role of miRNA as predictors of response to therapy in MF/SS.
Funding sources L.Y.M. is supported by the Dermatology Foundation, and NIH/ NCI (K12CA090625), American Cancer Society (IRG-58-00951), NIH (UL1TR000445), and the Vanderbilt Department of Medicine/Dermatology. C.M.E. is supported by R01CA148950 and the Vanderbilt Department of Pathology, Microbiology and Immunology.
© 2014 European Academy of Dermatology and Venereology
