Table 4.
Markers positively or negatively associated with morBCC, with corresponding dermatopathological purpose. Information taken from https://www.pathologyoutlines.com/ unless otherwise specified (accessed on 11 August 2023).
| Marker | Function |
|---|---|
| AE1/AE3 | Immunoreactivity is observed in epithelia and most carcinomas |
| AR | Transcription factor facilitating the effects of androgens, expressed variably across breast cancer subtypes |
| ARC | Neuronal differentiation marker [48] |
| Bcl-2 | Prevents cells from undergoing apoptosis |
| BerEp4 | Membranous staining; antibody to cell membrane glycoproteins expressed on healthy epithelia and in various carcinomas |
| c-Met | Activates various signaling pathways that lead to proliferation and cell survival |
| CD23 | To differentiate small lymphocytic lymphoma/chronic lymphocytic leukemia from mantle cell lymphoma or MALT lymphoma; B cell marker |
| CD34 | Distinguish Kaposi sarcoma, dermatofibrosarcoma protuberans, and epithelioid sarcoma from dermatofibroma; distinguish solitary fibrous tumor from desmoplastic mesothelioma; distinguish hemangiopericytoma from endometrial stromal sarcoma |
| cerbB2 | Crucial role in cell growth and division, specifically associated with HER2+ breast cancer |
| CK15 | Downregulated in activated keratinocytes in psoriasis, hypertrophic scars, and skin injury; normal positive staining in nail, hair follicle bulge, and follicular stem cells; positive staining in trichoepithelioma |
| CK17 | Basal type cytokeratin of complex epithelia; positive staining in basal cell carcinomas, hair shaft epithelia, and sebaceous glands |
| CK19 | Present in simple and complex epithelium; positive staining in hair follicles; negative stain in trichilemmoma |
| CK20 | Epithelial marker; positive staining in Merkel cell carcinoma and fibroepithelioma of Pinkus |
| CK34βE12 | Positive staining in classic and basaloid squamous cell carcinoma, as well as amyloid deposits associated with squamous cell carcinoma and dysplasia in the head and neck |
| CK8 | Used to confirm epithelial nature of tissue/tumors |
| COL1A1 | Major component of type I collagen, overexpressed in many cancers across numerous cellular processes [58] |
| COX-2 | Positive staining in skin cancers |
| D2-40 | Mostly used to show lymphatics (e.g., lymphovascular invasion) and lymphatic differentiation in vascular tumors; positive in primary skin adnexal tumors |
| E-cadherin | Transmembrane protein involved in cellular adhesion and polarity maintenance; loss is associated with gain of tumor cell motility and invasiveness |
| EMA | Absent in normal epithelia, but highly positive staining in most carcinomas |
| Ezrin | Links the cell membrane and the actin cytoskeleton; cell adhesion to the extracellular matrix, cell–cell communication, signal transduction, and apoptosis; active role in regulating tumor growth and progression and metastatic dissemination of many cancers [39] |
| FOXP3 | Plays an essential role in maintaining homeostasis of the immune system by regulating the suppressive function, stability, and expansion of Tregs; facilitates tumorigenesis by enabling tumor cells to evade antitumor immunity by inhibiting T-cell proliferation |
| GAP-43 | Neuronal differentiation marker [48]; display intrinsic oncogenic functions [59] |
| GLI1 | Important transcriptional regulator within the Hh signaling cascade [60]; specifically expressed in the bulb areas of hair follicles [61] |
| GLI2 | Essential for embryonic hair follicle development [62] |
| gp38 | Mucin-type protein upregulated in several squamous cell carcinomas, along with their corresponding CAFs [63] |
| HGF/SF | Expressed by myofibroblasts [33]; stimulates motility and invasiveness of epithelial and cancer cells [64] |
| IGF-1R | Highly overexpressed in various carcinomas, promoting cell survival through its function as an antiapoptotic agent [65] |
| IMP3 | Cytoplasmic marker with expression in many malignancies; tendency of higher expression in more aggressive neoplasms |
| Ki-67 | Marker of cell proliferation; increased in most malignant and inflammatory conditions |
| Lgr5 | Hair follicle stem cell marker [50] |
| Ln-γ2 | Marker of invasive tumors; frequently expressed in malignant tumors [32] |
| Lrig1 | Positive prognostic marker in Merkel cell carcinoma [66] |
| Maspin | Product of a tumor suppressor gene; involved in apoptosis and inhibition of carcinoma invasion, metastasis, and angiogenesis; expression is downregulated during cancer progression [39] |
| p16 | Tumor suppressor protein |
| p40 | Stimulates cell proliferation, blocks apoptosis, and favors unrestrained tumor growth |
| p53 | Tumor suppressor gene |
| p63 | Regulates human keratinocyte proliferation; myoepithelial marker; does not appear to be a tumor suppressor gene |
| P75NTR | Controlling the survival and process formation of neurons [67] |
| PCNA | Role in DNA synthesis, DNA repair, and cell cycle progression; expression correlates with proliferation activity |
| PD-L1 | Immune checkpoint protein expressed on activated immune cells and tumor cells; coinhibitory factor to regulate the immune response and limit autoimmunity; adaptive resistance mechanism to avoid T cell mediated anticancer immune response |
| PHLDA1/TDAG51 | Tumor suppression; to differentiate trichoepithelioma from BCC |
| ProEx C | Helpful in distinguishing melanoma from benign nevi; useful proliferation marker for high-grade vulvar or cervical intraepithelial neoplasia [68,69] |
| S-100 | Tumor marker of metastatic melanoma, along with clear cell sarcoma of soft tissue and myoepithelial tumors |
| SMA | Identifies pericytes, myoepithelial cells, smooth muscle cells and myofibroblasts in normal, reactive, or neoplastic tissue; immunoexpression may predict aggressive behavior in cutaneous basal cell carcinoma |
| SOX-9 | Transcription factor linked to hedgehog pathways, plays a central role in development and differentiation of multiple cell lineages |
| αvβ6 | Regulate epithelial remodeling during development, tissue repair, and neoplasia; associated with a more aggressive phenotype [70] |
| β-catenin | Mutations and overexpression of β catenin are associated with various carcinomas; plays an important role in the cadherin/catenin complex dynamics involved in cell–cell adhesion, the loss of which may lead to tumor invasion and metastasis [71] |
| β-tubulin III | Neuronal differentiation marker [48]; frequently overexpressed in human tumors and associated with tumor aggressiveness [72] |