Trop2 Expression in Extramammary Paget’s Disease and Normal Skin

Ito, Takamichi; Tanegashima, Keiko; Tanaka, Yuka; Hashimoto, H.; Murata, Maho; Oda, Yoshinao; Kaku-Ito, Yumiko

doi:10.3390/ijms22147706

Cited by 11 publications

(11 citation statements)

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“…We previously reported TROP2 expression in normal skin and skin appendages [11] and detected strong TROP2 expression in sebaceous and sweat glands. These findings prompted us to further investigate TROP2 expression in sebaceous carcinoma and sweat gland carcinoma.…”

Section: Introductionmentioning

confidence: 88%

“…Trophoblast cell surface antigen 2 (TROP2) is a surface glycoprotein originally identified in human placental trophoblasts [3][4][5]. TROP2 is highly expressed in various cancers such as pancreatic cancer [6], gastric cancer [7], lung cancer [3], colorectal cancer [8][9][10], and extramammary Paget's disease [11]. Because TROP2 is involved in various malignant tumor processes including cancer proliferation, migration, invasion, and metastasis and TROP2 overexpression is associated with worse patient survival in several solid malignant tumors, TROP2 has attracted attention as a potential target for cancer therapy [9,[12][13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

Ito

Hashimoto

Tanaka

et al. 2022

JCM

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Sebaceous carcinoma and sweat gland carcinoma (malignant tumors with apocrine and eccrine differentiation) are rare malignant skin adnexal tumors that differentiate toward sebaceous gland and eccrine and apocrine glands, respectively. Owing to the rarity of these carcinomas, standard treatments for advanced disease have not been established. Because the prognosis of patients with systemic metastasis is poor, a new treatment for these diseases is eagerly desired. Trophoblast cell surface antigen 2 (TROP2) and sacituzumab govitecan, an antibody–drug conjugate of TROP2, have attracted attention in the treatment of various solid tumors. In the current study, we immunohistochemically investigated TROP2 expression in 14 sebaceous carcinoma and 18 sweat gland carcinoma samples and found strong and relatively homogeneous TROP2 staining in both cancer types. The mean Histoscore, a semi-quantitative scoring ranging from 0 (negative) to 300, was 265.5 in sebaceous carcinoma and 260.0 in sweat gland carcinoma. These observations directly suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with TROP2-targeted antibody–drug conjugates such as sacituzumab govitecan.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

Ito

Hashimoto

Tanaka

et al. 2022

JCM

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“…Alopecia is the most common dermatologic toxicity, followed by a poorly characterized maculopapular cAE 28–31,60,259 . High expression of TROP2 in keratinocytes and the inner root sheaths and the infundibulum/isthmus of hair follicles most probably contributes to these toxicities 260 . Table 2 lists the types of dermatologic toxicities seen with mAbs targeting TROP2.…”

Section: Resultsmentioning

confidence: 99%

The diverse landscape of dermatologic toxicities of non‐immune checkpoint inhibitor monoclonal antibody‐based cancer therapy

et al. 2022

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Background Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non−immune checkpoint inhibitor (non‐ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. Methods A comprehensive review was conducted on dermatologic toxicities associated with different classes of non‐ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta‐analyses; and case series/reports. Results Dermatologic toxicities were associated with several types of non‐ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non‐ICI mAbs. Immunobullous reactions were rare and a subset of non‐ICI mAbs were associated with the development of vitiligo cAEs. Conclusion Dermatologic toxicities of non‐ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non‐ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

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“…Sections were conducted by HIER (CC1) for 32 min and incubated for 16 min with anti-TROP2 in the autoimmunostainer. Normal skin tissue was used for positive control and normal cerebral cortex was used for negative control of TROP2 immunostain (Supplementary Figure 1 ) [ 22 , 23 ]. Immunostained slides were scanned on a PANNORAMIC 250 Flash III (3DHISTECH, Budapest, Hungary) with PANNORAMIC Scanner Software (3DHISTECH, Budapest, Hungary).…”

Section: Methodsmentioning

confidence: 99%

Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer

Jeon

Hong

et al. 2022

BMC Cancer

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Background Trophoblast cell-surface antigen 2 (TROP2) is related to tumor proliferation enhancement and poor prognosis. An antibody targeting TROP2 was developed to treat metastatic triple-negative breast cancer (TNBC) which has a limited treatment modality. To characterize the TROP2 expressing tumors in TNBC, we analyzed TROP2 expression in three cohorts; (1) primary tumor without neoadjuvant chemotherapy, (2) primary tumor with neoadjuvant chemotherapy, and (3) metastatic tumor. Methods A total of 807 TNBC cases were evaluated for TROP2 immunohistochemical expression. We evaluated the TROP2 H-score distribution in the three cohorts. Tumors were divided into two groups based on TROP2 expression (high vs. low). We analyzed the relationship between clinicopathologic features and markers, including epidermal growth factor receptor, cytokeratin 5/6, p53, and Ki-67, and prognostic significance at high vs. low TROP2 expression. Results There was no difference in TROP2 H-score distribution between the three cohorts. Moderate-to-strong membranous expression of TROP2 in at least 10% of tumor cells was present in 662 cases (82.0%) in Cohort 1, 59 cases (89.4%) in Cohort 2, and 23 cases (88.5%) in Cohort 3. There was no significant difference in clinicopathologic features between high vs. low TROP2 in all cohorts. TROP2 H-score was an independent poor prognostic factor for overall survival in Cohort 3. Conclusions TNBC showed similar TROP2 expression regardless of neoadjuvant treatment or primary tumor/metastasis. Although the prognostic significance of TROP2 expression in metastatic TNBC has been revealed, further evaluation of the predictive value of TROP2 expression for targeted therapy is needed.

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Trop2 Expression in Extramammary Paget’s Disease and Normal Skin

Cited by 11 publications

References 48 publications

TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

The diverse landscape of dermatologic toxicities of non‐immune checkpoint inhibitor monoclonal antibody‐based cancer therapy

Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer

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