Joy King

Verrucous sarcoidosis associated with human papillomavirus infection: A case report

Verrucous sarcoidosis (VS) is a rare variant of cutaneous sarcoidosis that most often appears on the lower extremities. It could represent a localized hypertrophic response over an area with underlying noncaseating sarcoidal granulomas or a response secondary to a viral wart overlying a sarcoidal plaque. A case of annular VS on the face is reported in the setting of widespread background cutaneous papular and plaque sarcoidosis.

Punctate Follicular Porokeratosis: Clinical and Pathologic Features

Porokeratosis is a disorder of keratinization characterized by an abnormal cornoid lamella surrounding an annular, scaly plaque with an atrophic center. A histologic variant of this condition has been proposed, termed follicular porokeratosis, in cases where follicular involvement was contiguous with an annular cornoid lamella. There has been only 1 report of punctate follicular porokeratosis, in which cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. The authors present the second case of punctate follicular porokeratosis, further supporting the contention that this entity is a unique form of porokeratosis rather than a histologic variant. A 56-year-old African American female presented to the dermatology clinic with a 3-month history of keratotic lesions localized on the right posterior shoulder. Examination revealed an area of perifollicular keratotic papules, each surrounded by an erythematous rim. Histopathology revealed a cornoid lamella originating within a hair follicle, with the parakeratotic column protruding through the follicular orifice. The static nature of the condition along with exclusive involvement of hair follicles supports the notion of punctate follicular porokeratosis as a distinct clinical entity. The diagnosis of this condition relies heavily on proper histopathologic sampling revealing punctate follicular cornoid lamellae.

Infraorbital cutaneous horn

A 53-year-old African American woman presented with a left infraorbital lesion that had enlarged over several years. Two dozen brown papules had been present bilaterally on her cheeks for the past 8 years. The physical examination revealed a 2-mm diameter cutaneous horn that was 1.2 cm in length and 24 brown, homogenous colored 1-mm papules on her cheeks and eyelids (Fig 1). The lesion was completely removed using the shave biopsy technique at the base, which revealed the histopathologic features shown below (Figs 2 and 3).

Abstract 4918: Emerging prognostic biomarkers in colorectal cancer: HURP and ZEB1

The current diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to different genetic and epigenetic backgrounds. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Stem-like molecules have the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N = 21) obtained from colectomies and 5 μm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N = 8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher (p = 0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase (p = 0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christopher Lahr, Christian R. Gomez. Emerging prognostic biomarkers in colorectal cancer: HURP and ZEB1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4918.

Abstract B03: HURP and ZEB1: Novel prognostic biomarkers in colorectal carcinomas

The current clinicopathologic diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to the different genetic and epigenetic backgrounds not currently incorporated into CRC staging which can ultimately lead to treatment failure. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Recently, we and others have identified “stem-like” molecules with the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N=21) obtained from colectomies and 5 µm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N=8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher ( p =0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase ( p =0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p p value = 0.387. Any conclusions about population-based distribution of poor prognosis with regards to ZEB1 positive CRC will require an adequately powered sample size. Overall, we have identified two stem cell-like molecules, HURP and ZEB1, with potential as markers of aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christian R. Gomez, Christopher Lahr. HURP and ZEB1: Novel prognostic biomarkers in colorectal carcinomas. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B03.

Abstract P4-06-04: Gamma-secretase inhibitors suppress the activation of NFκB and the expression of TNFα, IL-6 and IL-8 in triple negative breast cancer cells

Background: Inflammation mediators, such as NF-kappa B (NFκB) and tumor necrosis factor alpha (TNFα), play major role in breast cancer pathogenesis, progression, and relapse. Triple negative breast cancer (TNBC) is a heterogeneous group of aggressive breast cancers and often has a poor outcome, in which Notch pathways are highly activated. However, role of crosstalk between Notch and inflammation mediators in TNBC progression and recurrence is poorly understood. The present study determines: 1) whether NFκB is highly activated in TNBC cells such as MDA-MB-231 (claudin-low-like) and MDA-MB-468 (basal-like), compared to ER-positive cells (MCF-7); 2) whether TNFα, IL-6 and IL-8 are highly expressed in TNBC cells, compared to MCF-7 cells; 3) whether Notch inhibition by gamma-secretase inhibitors (GSIs) significantly decrease NFκB activation and the expression of TNFα, IL-6 and IL-8 in TNBC cells; 4) whether GSI inhibits TNBC cell migration. Material and Methods: MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. The cells were exposed to GSIs such as DAPT and RO4929097 for 18 hours. Nuclear NFκB activation was determined by using the TransAM NFκB p65 kit (Active Motif). The expressions of TNFα, IL-6, IL-8, and IFNγ were determined by the ELISA kits (RD and 2) Notch inhibition by GSIs significantly decrease NFκB activation and the expression of TNFα, and IL-8 in TNBC cells. These results support the hypothesis that the crosstalk between Notch and NFκB lead to activation of inflammation mediators such as TNFα and IL 8, which contribute to TNBC progression and recurrence. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-04.