Mutually Exclusive Expression of COL11A1 by CAFs and Tumour Cells in a Large panCancer and a Salivary Gland Carcinoma Cohort

AbstractProcollagen 11A1 (COL11A1) is a central component of the extracellular matrix in many carcinomas, which is considered to be mainly produced by cancer associated fibroblasts (CAFs). As COL11A1 expression correlates with adverse prognosis and is implicated in chemoresistance, it is a promising putative target. For the first time, we used RNA in-situ hybridization to systematically identify the cells that produce COL11A1 in the ten most prevalent carcinoma types, lymphomas (n = 275) and corresponding normal tissue (n = 55; panCancer cohort). Moreover, as most salivary gland carcinomas (SGC) display distinct stromal architectures, we also analysed 110 SGC. The corresponding protein formation of COL11A1 was determined by MALDI-TOF–MS-Imaging. We report that colon, breast and salivary duct carcinomas are highly infiltrated by COL11A1 positive CAFs (CAFsCOL11A1) and might thus be promising candidates for antidesmoplastic or COL11A1-targeted therapies. The amount of CAFsCOL11A1 correlated significantly with tumour grade, tumour stage and nodal spread in the panCancer cohort. Significant associations between CAFsCOL11A1 and vascular invasion, perineural spread and nodal spread were observed in the SGC cohort. Also, we discovered that tumour cells of intercalated duct derived SGC and CAFs produce COL11A1 in a mutually exclusive manner. Our findings represent a novel mode of extracellular matrix production in carcinomas and could be highly relevant in the future. Our findings elucidate the mode of COL11A1 expression in very different carcinoma types and may aid to categorise tumours in the setting of possible future COL11A1-related therapies.

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Fluorouracil, doxorubicin, cyclophosphamide, and cisplatin combination chemotherapy in advanced or recurrent salivary gland carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.6.1056 ◽

1990 ◽

Vol 8 (6) ◽

pp. 1056-1062 ◽

Cited By ~ 54

Author(s):

I W Dimery ◽

S S Legha ◽

M Shirinian ◽

W K Hong

Keyword(s):

Salivary Gland ◽

Response Rate ◽

Objective Response ◽

Response Duration ◽

Hematologic Toxicity ◽

Minor Response ◽

Therapeutic Trials ◽

Salivary Gland Carcinomas ◽

Gland Carcinoma ◽

A Minor

Seventeen patients with recurrent or unresectable salivary gland carcinomas were treated with combination fluorouracil (5-FU), doxorubicin, cyclophosphamide, and cisplatin (FACP). Sixteen patients were assessable for response and toxicity. A total of 111 courses of chemotherapy were given, yielding one complete and seven partial responses, for an objective response rate of 50%. Two other patients had stable disease and two had a minor response. The median duration of objective response was 32 weeks (range, 4 to 72); median survival for the 16 patients was 72 weeks. Hematologic toxicity was significant, with 88% developing a nadir granulocyte count of less than 1,000 cells per microliter (median, 300 cells per microliter), and 53% a nadir platelet count of less than 100,000 cells per microliter (median, 68,000 cells per microliter). Seven patients (44%) developed neutropenic fever, and three (18%) developed an increase in serum creatinine greater than 1.5 mg/dL during the course of treatment. This combination of chemotherapy was active; however, an increased response rate was not observed above that reported for other combinations. Response duration, or overall patient survival, on this intensive regimen was similar as compared with other published therapeutic trials of this disease entity.

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Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target

Head and Neck Pathology ◽

10.1007/s12105-021-01325-5 ◽

2021 ◽

Author(s):

Philipp Wolber ◽

Lisa Nachtsheim ◽

Franziska Hoffmann ◽

Jens Peter Klußmann ◽

Moritz Meyer ◽

...

Keyword(s):

Salivary Gland ◽

Cell Surface ◽

Surface Antigen ◽

Treatment Options ◽

Trophoblast Cell ◽

Cell Surface Antigen ◽

Antibody Drug Conjugate ◽

Ms Imaging ◽

Salivary Gland Carcinomas ◽

Antibody Drug

AbstractTreatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody–drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody–drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.

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