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. 2025 Jul 8;54(8):658–666. doi: 10.1111/jop.70008

TROP2 Expression in Salivary Gland Adenoid Cystic Carcinoma (ACC) According to Histologic Subtype: Therapeutic Implications

Juliana Mota Siqueira 1,2, Yoshitsugu Mitani 3, Mario L Marques‐Piubelli 4, Camilla Oliveira Hoff 1, Flavia Bonini 1, Luana Guimaraes de Sousa 1, Mutsumi Mitani 1, Giovanna Lopes Carvalho 2, Fabio Daumas Nunes 2, Leandro Luongo Matos 5, Shiaw‐Yih Lin 6, Michael T Spiotto 7, Ehab Y Hanna 8, Daniel J McGrail 9, Adel K El‐Naggar 3, Renata Ferrarotto 1,✉
PMCID: PMC12419983  PMID: 40624990

ABSTRACT

Background

Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2‐antibody–drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods

TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non‐solid, solid + non‐solid, or solid. TROP2 protein expression in ACC cell lines was assessed and subjected to drug screening with TROP2‐ADC.

Results

TROP2 expression was high in 59%, moderate in 30%, weak in 8%, and negative in 3% of cases. TROP2 expression was significantly higher in non‐solid compared with solid or solid + non‐solid (p < 0.001). Notably, TROP2 expression was heterogenous among the dual cellular component, with TROP2 expression identified predominantly in the ductal and not in the myoepithelial cells. In vitro drug screening demonstrated that TROP2‐ADC had selective anti‐tumor effect in TROP2 expressing ACC cells.

Conclusions

TROP2 expression is prevalent in ACC, particularly in the ductal cell component of the non‐solid tumors. The pre‐clinical drug screening findings provide a biological rationale for exploring TROP2 as a therapeutic target in TROP2‐expressing ACC.

Trial Registration

clinicaltrials.gov: NCT05884320; NCI‐2023‐04260

Keywords: ADC, adenoid cystic carcinoma, antibody–drug conjugate, immunohistochemistry, sacituzumab govitecan, SN‐38, TROP2

1. Introduction

Adenoid cystic carcinoma (ACC) is a secretory gland carcinoma (SGC) that commonly affects minor and major salivary glands [1, 2, 3]. Histologically, ACC neoplastic cells exhibit luminal epithelial (ductal) or myoepithelial differentiation [4]. The distribution and predominance of epithelial and myoepithelial cells varies depending on the tumor's growth pattern: cribriform, tubular, or solid (S) [5]. Although tubular and cribriform patterns predominate myoepithelial cells, S histology is typically characterized by epithelial cell predominance [4, 5]. Normally, ACC tumors are highly heterogeneous, with multiple growth patterns represented in a single tumor [6]. Of note, the presence of any S growth is associated with poor prognosis [6].

Although typically slow growing, ACC is locally aggressive and has a high propensity to recur and/or metastasize after curative intent treatment [1, 7, 8, 9]. Treatment options for recurrent or metastatic (R/M) disease are scarce and not well established, and there is no FDA‐approved systemic therapy [10]. ACC is overall chemotherapy (CT) refractory, with overall response rates ranging between 10%–20% for most platinum‐based regimens [11]. Other systemic therapies are multikinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR). Still, their efficacy results have been similar to those seen with CT, and the impact on overall survival (OS) is unclear [12, 13, 14, 15, 16, 17].

Genomic and proteomic advancements have transformed the understanding of ACC tumor biology and is guiding the development of targeted therapies for R/M patients [18, 19]. Although the majority of ACC harbor a translocation t(6:9) (MYB‐NFIB) [20], further proteogenomic analysis of ACC has identified two distinct subtypes, ACC‐I and ACC‐II [19]. ACC‐I is characterized by NOTCH pathway activation and MYC overexpression, predominantly represented by S tumors, and usually have an aggressive behavior with a median OS of 3.44 years. In contrast, ACC‐II is marked by TP63 upregulation, mostly consisting of tubular and cribriform patterns, and exhibit a more indolent behavior with a median OS of 23.2 years [19]. Notably, subtype‐specific therapeutic targets have been identified and are being explored [21, 22, 23, 24].

Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein encoded by TACSTD2 gene. It was initially identified in human placental tissue and further found to be involved in oncogenic pathways of several cancer types [25]. The prognostic value of TROP2 expression varies by cancer type, reflecting its presence in normal precursor cells. High TROP2 levels indicate aggressiveness and poor prognosis in tumors from TROP2‐negative precursors, whereas its loss in tumors from TROP2‐positive precursors is linked to progression and worse outcomes [26, 27].

Sacituzumab govitecan (SG; Trodelvy, Gilead Sciences Inc., Foster City, CA) is an anti‐TROP2 antibody–drug conjugate (ADC) approved by the FDA for treating unresectable locally advanced or metastatic triple‐negative breast cancer. SG has demonstrated significant clinical benefits, promoting longer OS compared with standard CT in breast cancer patients [28]. Therefore, several clinical trials are investigating SG in other tumor types, with encouraging interim results [29]. Considering the lack of established systemic therapies that provide substantial benefits in ACC and the complex road to developing new drugs, research into potential targetable molecules with approved drugs is remarkably valuable. Here, we assessed TROP2 expression in ACC according to the different histologic growth patterns and explored its relevance as a potential therapeutic target.

2. Materials and Methods

2.1. Patient Cohort

This study included patients diagnosed with ACC at the University of Texas MD Anderson Cancer Center between July 1978 and October 2006 with available formalin‐fixed paraffin‐embedded surgical resection specimens. Clinical and pathological reports from medical records were reviewed for patient and tumor characteristics.

The RNA‐seq cohort comprised two cohorts of ACC with available RNA‐seq data collected as part of previous studies. After removing duplicate samples, 37 samples from our group [19] were available for analysis in Cohort 1 and 45 from Frerich et al. [30] in Cohort 2.

This study was carried out in accordance with the Declaration of Helsinki and approved by the institutional review board.

2.2. Tissue Samples and IHC Staining

For tissue microarrays (TMA) construction, a semi‐automated precision instrument was used to punch out two cores of 1‐mm diameter of the representative growth patterns in each case and placed into empty recipient paraffin blocks. Normal salivary gland and spleen tissue were used as positive and negative controls, respectively. Four micrometer–thick sections were used for immunohistochemistry (IHC) for TROP‐2, using the Automated Leica Bond III Staining platform (Leica Biosystems, Germany). An anti‐TROP2 rabbit IgG monoclonal antibody (EPR20043 clone, Abcam, Cambridge, United Kingdom, #214488) in 1:4000 dilution was validated and optimized.

Two pathologists (J.M.S. and M.L.M.‐P.) unawate of the patient's clinical outcomes to the patient's clinical details manually and independently evaluated the stained slides. Discordant cases were reviewed by a third pathologist (A.K.E.‐N.). Tumor cell membrane TROP2 expression was categorized using a semiquantitative score based on the percentage of stained tumor cells. The intensity of positive cases' staining was divided into weak (1+), moderate (2+), and strong (3+) based on the intensity of positive controls.

For the statistical analysis, the following TROP2 expression categories were used: negative (< 1% of any intensity), weak (≤ 70% of weak or ≤ 30% of moderate expression), moderate (> 70% of weak or > 30% of moderate or ≤ 30% of strong expression), and high (> 70% of moderate or > 30% of strong expression) [26, 27]. When appropriate, binary analysis between high versus non‐high (negative, weak, or moderate) was considered for clinical associations.

Due to the histological heterogeneity of ACC, mixed growth patterns could be found between two cores of the same tumor and inside the same tumor core. To account for these characteristics, histologic subtype was grouped as non‐solid (nS; tubular and/or cribriform), predominant S (S in more than 90% of tumor area), or S + nS (mixed patterns including S and tubular/cribriform). Additionally, IHC for P63 (dilution 1:100, clone 4A4; catalog number CM163C; Biocare), a standard myoepithelial marker, was performed to characterize the bicellular composition of ACC and assess for association with TROP2 expression.

2.3. RNA‐Seq Deconvolution Analysis

The 82 ACC samples with available RNA‐seq were classified as ACC‐I and ACC‐II based on z‐normalized MYC and TP63 gene expression levels (MYC minus TP63), as previously described [19]. Differential expression of TACSTD2 (TROP2) was determined using rank–sum test.

2.4. ACC Cell Lines

ACC cell lines, MDA‐ACC‐01 [31] and MDA‐ACC‐23 (recently established, manuscript submitted) were maintained in rich DMEM medium (Life Technologies) containing 10% fetal bovine serum (Life Technologies), 1% penicillin–streptomycin (Life technologies), 5 ng/mL epidermal growth factor (Sigma–Aldrich), 0.4 μg/mL human hydrocortisone (StemCell Technologies) and 5 μg/mL human insulin (Sigma–Aldrich). ACC‐R9f1 cell line derived from PDX‐organoid (short‐term cultivation) was maintained in a 1:1 mix of rich DMEM and salivary gland organoid medium. All cell lines grow at 37°C and 5% CO2 in a humidified incubator by standard cell culture techniques.

2.5. In Vitro Drug Screening

The cells were split at 3000 cells/well in 96‐well plates. Various concentrations of SG (Selleck Chemicals) or its payload SN‐38 (Selleck Chemicals) were applied to cells after 24–48 h of seeding (0 day), and then cell proliferation was monitored at 3 days using CellTiter‐Glo 2.0 (Promega). Drug screening was performed independently in triplicate. GR50 (cell growth rate inhibition by 50%) was calculated using the GRmetrics (version 1.28.0) in Bioconductor R package [32].

2.6. Western Blot Analysis

Whole‐cell lysate protein was extracted from cell lines using RIPA buffer with freshly added protease inhibitor (Roche Applied Science) and phosphatase inhibitor (Roche Applied Science) cocktails. Twenty micrograms of protein samples were loaded and separated by SDS‐PAGE gel electrophoresis, and then protein was transferred onto a nitrocellulose membrane using the Trans‐Blot Turbo Transfer System (Bio‐Rad), according to the manufacturer's instructions. The membrane was incubated with primary antibodies, anti‐TROP2 (rabbit, Abcam, #214488), anti‐cleaved PARP (rabbit, Cell Signaling, #5625) and anti‐beta actin (mouse, Sigma–Aldrich, #A5316) antibodies.

2.7. Statistical Analysis

Statistical analyses were performed with GraphPad Prism 9.0 (GraphPad Software Inc., San Diego, CA) and R Statistical software (version 2.14.0; R Foundation for Statistical Computing, Vienna, Austria). Normality tests (Shapiro–Wilk) and manual review of Q–Q plots were performed to assess the distributional assumptions. Contingency tables and the Fisher exact test were applied as appropriate to identify associations between TROP2 immunostaining and clinicopathological characteristics. Simple linear regression was used to determine gene correlations. The Kaplan–Meier method assessed OS estimated from the date of diagnosis. The log‐rank test was applied to detect significant differences between groups. A p value of ≤ 0.05 was considered statistically significant.

3. Results

3.1. Patient Cohort Characteristics

After excluding noninterpretable samples due to loss of tissue, a total of 165 samples of patients with ACC were evaluated. Patient clinicopathologic characteristics are depicted in Table 1. Female patients composed 53% of the cohort, and the mean age at diagnosis was 52.7 years (range: 15–79 years). Most patients presented with clinical stage I–III (36%) or IVA–IVB (35%) disease (AJCC Staging System, 7th edition) [33]. Primary tumors represented the majority of samples (88%), with minor salivary glands representing the most frequent primary site (64%).

TABLE 1.

Clinicopathologic characteristics by TROP‐2 expression.

Characteristic, n (%) Negative, n = 5 (3) Weak, n = 13 (8) Moderate, n = 49 (30) High, n = 98 (59) Statistics
Mean age (52.7 years)
Age, years
≤ 50 1 (20) 6 (46) 23 (47) 45 (46) Fisher's p = 0.90
> 50 4 (80) 7 (54) 26 (53) 53 (54)
Sex
Male 3 (60) 5 (38) 24 (49) 46 (47) Fisher's p = 0.91
Female 2 (40) 8 (62) 25 (51) 52 (53)
Site
Major salivary gland 0 (0) 1 (8) 9 (18) 28 (29) χ 2 = 6.42, p = 0.11
Minor salivary gland 4 (80) 9 (69) 34 (69) 59 (60)
Other 1 (20) 3 (23) 6 (12) 11 (11)
Perineural invasion
Yes 4 (80) 6 (46) 34 (69) 74 (76) χ 2 = 5.17, p = 0.15
No 0 (0) 2 (15) 1 (2) 6 (6)
Unknown 1 (20) 5 (38) 14 (29) 18 (18)
TNM stage
I–III 1 (20) 3 (23) 19 (39) 37 (38) χ 2 = 7.63, p = 0.79
IVA–B 2 (40) 8 (62) 14 (29) 34 (35)
IVC 1 (20) 0 (0) 1 (2) 5 (5)
Unknown 1 (20) 2 (15) 15 (31) 22 (22)
Tumor origin
Primary 5 (100) 13 (100) 45 (92) 91 (93) χ 2 = 1.49, p = 0.68
Recurrent 0 (0) 0 (0) 4 (8) 7 (7)
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3.2. TROP2 Expression Is Prevalent in ACC Overall, but Higher in the Epithelial Cells of nS ACC

TROP2 membranous immunostaining was detectable in 160 cases (97%). Of note, strong expression of TROP2 was also found in normal salivary glands (Figure 1A). We observed predominantly high (59%) and moderate (30%) TROP2 expression; only 13 tumors (8%) weakly expressed TROP2, and five (3%) were negative.

FIGURE 1.

FIGURE 1

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Representative IHC images of TROP2 expression. (A) IHC for TROP‐2 in a normal salivary gland shows strong and uniform expression in seromucous acini. (B) High TROP2 expression in tubular ACC. (C) Predominantly moderate TROP2 pattern of staining in ACC. (D) Weak TROP2 expression in ACC. (E) Negative TROP2 expression in solid ACC. (F) When both solid and non‐solid components were present (S + nS), TROP2 expressed more in the non‐solid ACC areas. (G) Bar‐graph shows TROP2 expression by histologic subtype; high TROP2 expression was significantly associated with non‐solid (p < 0.0001). (H). Violin‐plot shows that TROP2 gene expression is upregulated in ACC tumors, with higher levels in ACC‐II than ACC‐I (p < 0.0001).

Analysis by histologic subtype revealed that high TROP2 expression was significantly associated with nS growth pattern (p < 0.0001) (Figure 1B–G). High TROP2 expression occurred in 73% of nS compared with 17% of S and 12% of S + nS. Moderate expression was found mainly in S + nS (64%) and weak expression was more frequent in S (33%) and S + nS histology (24%). TROP2 negatives were found exclusively in the S subtype (42%).

Interestingly, we noticed that when both S and nS components were present, TROP2 trended to express more in the nS areas (Figure 1F). In addition, transcriptomic analysis using our RNA‐seq [19] confirmed that TROP2 gene expression was significantly higher in ACC‐II, the ACC subtype more associated with nS histology, than ACC‐I (p < 0.0001) (Figure 1H).

Considering the heterogenous expression of TROP2 IHC (Figure 1) and dual cellular component of ACC (epithelial and myoepithelial cells), we further explored TP63 IHC (Figure 2). Interestingly, it was noted that myoepithelial cells, which are individually positive for p63, typically exhibit a negative expression for TROP2 (Figure 2).

FIGURE 2.

FIGURE 2

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TROP2 expression was identified in epithelial cells of ACC, but not in myoepithelial cells. Individual myoepithelial cells positive for P63, typically exhibit a negative expression for TROP2.

3.3. TROP2 Associations With Clinicopathological Parameters and Survival

No significant association was found between TROP2 expression and the clinicopathological characteristic evaluated, including age (p = 0.90), sex (p = 0.91), primary site (p = 0.11), perineural invasion (p = 0.15), or clinical stage (p = 0.7).

For OS analysis according to TROP2 expression, we first considered the four score groups (negative, weak, moderate, high) and did not find a significant association between TROP2 IHC expression and survival (p = 0.46) (Figure S1). Next, we grouped all patients with any loss of TROP2 expression (moderate, weak and negative) and compared with high TROP2 expression, which also demonstrated no association between TROP2 high expression and OS (HR 1.067, 95% CI: 0.73–1.55, p = 0.20) (Figure 3).

FIGURE 3.

FIGURE 3

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ACC overall survival by TROP2 expression. Survival analysis by Kaplan–Meier demonstrated that TROP2 expression is not prognostic in ACC with a median OS of 131 months for high TROP2 expression versus 106 months for non‐high (moderate/low and negative) (p = 0.20).

3.4. In Vitro TROP2‐ADC Treatment Effect in ACC Lines

TROP2 protein expression in ACC cell lines (ACC‐01, ACC‐23, and ACC‐R9f1) was assessed by Western blot (Figure 4A) and weak TROP2 expression was identified in ACC‐R9f1 cell in comparison to MAC cell lines (derived from salivary mucinous adenocarcinoma) [34]. We evaluated the effect of the TROP2 ADC SG on cell proliferation (Figure 4B). ACC‐R9f1 (TROP2 weak expression) demonstrated cell growth inhibition under SG treatment (GR50; 389 nM, Figure 4B), whereas no growth inhibition was found in the ACC‐01 TROP2 negative cell line (GR50; not available, Figure 4B). Notably, both ACC‐R9f1 and ACC‐01 cells were inhibited effectively by SN‐38, the payload of SG (GR50; 0.0232 and 0.0106 μM, respectively, Figure 4C); suggesting that TROP2 expression is important for TROP2‐ADC activity.

FIGURE 4.

FIGURE 4

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TROP2 Expression in ACC lines and TROP2 antibody–drug conjugate in vitro screening. (A) TROP2 expression by Western blot in ACC cell lines. MAC cell was used for positive control as TROP2 high expression. Beta‐actin (ACTB) was used as an internal loading control. (B) Sacituzumab govitecan, (SG) showed anti‐tumor effect in TROP2‐positive ACC‐R9f1 line, but not in TROP2‐negative ACC‐01 cells. (C) SN‐38 showed anti‐tumor effect in both ACC‐R9f1 and ACC‐01 cells regardless of TROP2 expression status. (D) Cleaved PARP expression after SG and SN‐38 treatments. SG demonstrated more selective anti‐tumor effect against TROP2‐positive ACC‐R9f1 than SN‐38.

We also assessed the apoptosis marker cleaved PARP after SG and SN‐38 treatments. The expression of cleaved PARP was increased in a dose‐dependent manner under SG treatment in ACC‐R9f1 cell, but not or faintly (at 1 μM) in ACC‐01 cell (Figure 4D). Under SN‐38 treatment, cleaved PARP expression in both ACC‐R9f1 and ACC‐01 also increased in a dose‐dependent manner, irrespective of TROP2 expression status (Figure 4D).

4. Discussion

In the current study, TROP2 gene and protein expression levels were assessed in a large ACC cohort. Remarkably, TROP2 expression was very prevalent in ACC in general (97%) and significantly higher in the nS, ACC‐II samples, representing the most common ACC subtype, suggesting the potential broad applicability of TROP2‐directed therapy in this population.

TROP2, also known as tumor‐associated calcium signal transducer 2 or EpCAM 2, is a cell surface receptor and plays a role in cell self‐renewal and proliferation [35]. Given its pronounced overexpression across numerous cancer types [36], TROP2‐directed drugs are being extensively investigated in clinical trials, culminating in the recent approval of the TROP2‐ADC SG by the FDA for the treatment of triple‐negative breast cancer and an accelerated approval for the treatment of advanced urothelial cancer [25, 28, 37].

Although anti‐TROP2 drugs are being explored in clinical trials for various types of cancers (Table S1), only two studies have endeavored to report the distribution of TROP2 in salivary gland carcinomas [26, 27]. The study by Dum et al. [26] evaluated TROP2 expression in over 150 tumor types, including 87 ACC, with 87.4% positive for TROP2. Wolber et al. [27] analyzed TROP2 expression in SGC of major salivary glands, primarily of the parotid gland (90.4%); among 22 ACC, 95.5% were TROP2 positive.

In our study, the expression of TROP2 was analyzed in a large cohort of 165 ACC tumors, taking into consideration the histological subtype and p63 expression, which are well‐established prognostic factors. We found that 89% of ACC exhibited moderate to high TROP2 expression, with only 11% showing weak or negative expression. These results align with Wolber et al.'s [27] study, where 81.9% of samples showed moderate to high TROP2 expression, and 18.1% were weak or negative. However, in Dum et al.'s [26] cohort, only 47% of ACC had moderate or high TROP2 expression. Despite equal score criteria used among these studies, sample size, distribution of ACC histologic subtypes, which was not reported in the other studies, and inter‐pathologist variability in IHC analysis may have accounted for the differences in the prevalence of TROP2 expression among cohorts. Furthermore, in our study, the histological analysis was performed in TMA, which, despite being a widely and efficiently used method, has limitations regarding representability.

The prognostic value of TROP2 expression in various cancer types has often been associated with the expression of TROP2 in normal precursor cells [26, 27]. Accordingly, in our study of ACC tumors, which arise from highly TROP2‐positive salivary gland precursor cells, high TROP2 expression tended toward more favorable survival outcomes, although it did not reach statistical significance (p = 0.20).

ACC histological pattern is widely acknowledged and validated as a strong prognostic factor in ACC. The aggressive ACC‐I transcriptomic subtype is predominantly represented by S histology, concomitant with the downregulation of the P63 gene and protein [19]. Accordingly, we verified through transcriptomic analysis that TROP2 was significantly lower in ACC‐I than in ACC‐II and positively correlated with P63 gene expression. Interestingly, our study demonstrated that TROP2 expression appears to be limited to epithelial cells when myoepithelial cells expressing P63 are present. This observation is noteworthy as most S tumors with an epithelial dominance exhibit a lack of TROP2 expression. This suggests a cross‐talk between neighboring cells, contributing to the intricate dual cell composition of ACC.

As normal salivary gland tissue expresses TROP2, there is a potential concern regarding the specificity of TROP2‐targeted therapies in ACC. However, clinical trials of SG in other malignancies have not shown significant toxicity to healthy salivary tissues, such as dry mouth or hyposalivation, although mucositis has been reported [38]. Given the high prevalence of TROP2 expression in ACC, we tested pre‐clinically its potential as a therapeutic target. We observed that the TROP2‐ADC SG induced cell growth inhibition in the TROP2 low expressing ACC line but not in the TROP2 negative cell, suggesting TROP2 expression may be important for SG anti‐tumor effect. Notably, SG uses a hydrolysable linker that allows for the release of the cytotoxic agent SN38 into the surrounding tumor microenvironment, creating a bystander effect [39]. This phenomenon may contribute to eliminating neighboring cells that do not overexpress TROP2, helping overcome tumor heterogeneity, a significant obstacle in ACC tumor treatment [40]. Considering this effect, it is reasonable to speculate that all ACC expressing TROP2, to some extent, could obtain benefits from this drug; indeed, in triple‐negative breast cancer, clinical benefit to SG was seen irrespective of TROP2 expression levels, although a correlation exists between higher expression levels and increased likelihood of objective responses [28].

To the best of our knowledge, this is the largest study evaluating TROP2 expression by IHC and RNA‐seq in ACC. In line with previous research, our findings revealed that a significant proportion of ACC tumors express TROP2, frequently at moderate or high levels. Adding novel insights, we demonstrated a higher prevalence of TROP2 in the nS, P63 positive, ACC‐II subtype, with expression predominantly in the epithelial tumor cells, which may aid in patient selection for TROP2‐targeted therapy. Together, these data support TROP2‐directed therapies in ACC, which is being investigated in a Phase II clinical trial.

Author Contributions

R.F. performed study concept and design. J.M.S. and Y.M. performed development of methodology. J.M.S., C.O.H., R.F., Y.M., L.G.S., M.L.M.‐P., D.J.M., M.T.S., E.Y.H., G.L.C., F.D.N., and L.L.M. performed writing, review and revision of the paper. J.M.S., Y.M., C.O.H., D.J.M., and F.B. provided acquisition, analysis and interpretation of data, and statistical analysis. A.K.E.‐N. confirmed and reviewed the pathology reports. All authors read and approved the final manuscript.

Ethics Statement

This study was conducted in accordance with the Declaration of Helsinki. Samples were obtained under The University of Texas MD Anderson Cancer Center (MDACC) Institutional Review Board (IRB) approved waiver of informed consent (for deceased patients) or informed consent for molecular and clinicopathologic analyses with approved IRB protocols (LAB10‐0918, PA‐17‐0865, and 2021‐0355).

Conflicts of Interest

Dr. Ferrarotto reports personal fees from Regeneron, Sanofi, Merck Serono, Elevar Therapeutics, Prelude Therapeutics, Eisai Inc., Remix Therapeutics, and Coherus BioSciences; nonfinancial support from Ayala Pharmaceuticals, EMD Serono, ISA, Genentech/Roche, Merck Serono, Pfizer, Viracta, and Gilead outside the submitted work. Dr. Sousa reports being the recipient of funds given to MD Anderson Cancer Center by Elevar Therapeutics, Agenus, and Regeneron in the last 36 months. Dr. Matos reports fees from MSD (HPV‐vaccine) not related to the present study.

Peer Review

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer‐review/10.1111/jop.70008.

Supporting information

Figure S1. Overall survival by TROP2 expression with the four groups. Survival analysis by Kaplan–Meier demonstrated that TROP2 expression is not associated with prognosis in ACC patients.

JOP-54-658-s001.jpg (354.4KB, jpg)

Table S1. Clinical trials with sacituzumab govitecan.

JOP-54-658-s002.docx (27.3KB, docx)

Acknowledgments

The authors thank Deborah A. Rodriguez for material retrieval and follow‐up information, and editing services, research medical library, for editing this article.

Siqueira J. M., Mitani Y., Marques‐Piubelli M. L., et al., “ TROP2 Expression in Salivary Gland Adenoid Cystic Carcinoma (ACC) According to Histologic Subtype: Therapeutic Implications,” Journal of Oral Pathology & Medicine 54, no. 8 (2025): 658–666, 10.1111/jop.70008.

Funding: This work was supported in part by DoD grant number (W81XWH‐21‐0409), Salivary Gland Tumor Biorepository (HHSN268200900039C 04), Adenoid Cystic Carcinoma Research Foundation, Wold Foundation, DeWayne Everage Adenoid Cystic Carcinoma Fund, Ryan Smith Adenoid Cystic Carcinoma Fund, and the Research Histology Core Laboratory (RHCL) support grant (NCI CA16672).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Figure S1. Overall survival by TROP2 expression with the four groups. Survival analysis by Kaplan–Meier demonstrated that TROP2 expression is not associated with prognosis in ACC patients.

JOP-54-658-s001.jpg (354.4KB, jpg)

Table S1. Clinical trials with sacituzumab govitecan.

JOP-54-658-s002.docx (27.3KB, docx)

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Articles from Journal of Oral Pathology & Medicine are provided here courtesy of Wiley

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