Adenocarcinoma NOS Research Articles

Immunohistochemical Expression of Mismatch Repair Proteins in Colorectal Carcinomas with Histopathological Correlation in a Quaternary Care Centre in South India

Background and Aims: Colorectal carcinomas are one of the most prevalent malignant neoplasms globally and are characterised by a range of genetic and epigenetic alterations, primarily chromosomal instability and microsatellite instability. This study aims to assess the expression of MMR proteins in patients with colorectal carcinoma and to examine the relationship between MMR status and various histopathological and clinical variables. Material and Methods: All biopsy and resection cases of colorectal carcinoma on which MMR was done by IHC were studied from December 2022 to November 2023. Histopathological and immunohistochemical assessments of mismatch repair proteins were done for 153 colorectal carcinoma patients in formalin-fixed paraffin-embedded tumour tissues. Statistical analysis was carried out using SPSS software (IBM, 28.0). Results: Out of 153 cases collected, 23 cases (15%) had a loss of MMR expression, and 130 cases (85%) had no loss of MMR protein. Combined loss of MLH1 and PMS2 was found in 16 cases (70%), combined loss of MSH2 and MSH6 was found in five cases (21%) and isolated loss of PMS2 was found in two cases (9%). Adenocarcinoma NOS, mucinous differentiation, medullary pattern, right-sided tumours, female gender and younger age group correlated with loss of MMR expression. Conclusion: Molecular study is the first approach for detecting MSI associated with CRC, IHC is a very good alternative to identify microsatellite instability. IHC methods can be used as a reliable tool in the workup for MSI as IHC markers (antibodies to the MMR proteins) are now easily accessible in most laboratories.

The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers.

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan-Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0-47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group.

Differential expression of epidermal growth factor receptor in various pathological types of salivary gland cancers

ObjectiveWhile several studies reported epidermal growth factor receptor (EGFR) expression in salivary gland cancer (SGC), results varied due to a lack of unified definition of EGFR positivity. In this study, we assessed the EGFR expression level using both EGFR positive score and cumulative EGFR score in the patients with SGC. MethodsBetween January 2010 and April 2021, 102 patients with SGC who underwent surgical resection were reviewed retrospectively by immunohistochemistry. The membrane staining intensity was scored as follows: no staining (0), weak staining (1+), intermediate staining (2+), and strong staining (3+). The cumulative EGFR score was determined on a continuous scale of 0–300 using the formula:1 × (1+: percentage of weakly stained cells) + 2 × (2+: percentage of moderately stained cells) + 3 × (3+: percentage of strongly stained cells). ResultsEGFR expression in SGC varied widely even among the same as well as different histopathological types. The average EGFR positive scores were 46.0 %, 55.7 %, 51.6 %, 1.0 %, 26.8 %, 50 %, and 76.8 % for mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma NOS (ACNOS), carcinoma ex pleomorphic adenoma (CAexPA), and squamous cell carcinoma (SqCC), respectively. The average cumulative EGFR scores were 82, 91, 80, 1, 52, 93, and 185 for MEC, SDC, AdCC, AcCC, ACNOS, CAexPA, and SqCC, respectively. ConclusionsEGFR positive scores and cumulative EGFR scores in SGCs varied among the various histological types, and even in the same histological type. These scores may predict the clinical outcome of SGC treated with EGFR-targeting therapies, such as head and neck photoimmunotherapy, and need to be evaluated in future studies.

Clinicopathological Evaluation of Gall-Bladder Lesions in Cholecystectomy Specimens with Special Emphasis to Incidentally Detected Cases of Gall-Bladder Carcinoma Along with Immunohistochemical Study of Cytokeratin 7 and Cytokeratin 20

Introduction: Cholecystectomy specimens show wide clinicopathological spectrum varying from common non neoplastic diseases to rare neoplastic lesions and histopathological examination the gold standard for final diagnosis. Gall Bladder Cancers (GBCs) are rare and account for 0.5% to 1.09% of all gall bladder lesions. It is either clinically suspected or incidentally diagnosed following cholecystectomy. Methods: It was a Hospital based cross-sectional Study. All cases diagnosed clinically & radiologically and operated as cholecystitis were included in the study. Histopathological diagnosis of gallbladder lesions, age & sex distribution in different gallbladder pathology, association with gall stones, Pathological pT staging of malignant cases and CK7 & CK20 immunohistochemical findings in malignant cases were observed in this study. Results: A total 340 cases of gallbladder specimens were examined histopathologically and 12 cases of gallbladder carcinoma were diagnosed. The most common histopathological diagnosis was chronic cholecystitis (79.4%) followed by chronic cholecystitis with cholesterolosis (7.6%) and adenocarcinoma (3.5%). The most common age group for gallbladder lesions was 4th decade (26.2%). Age varies from 09 – 85 years with a mean age of 39.4 years. Overall females (83%) are more commonly affected than males (17%) with male: female ratio is 1:4.96. Gallstones were present in 89.1% among total cases, 83.3% in malignant cases. Incidentally detected gallbladder carcinoma was 1.17% and most common histopathological type was adenocarcinoma NOS with Pathological pT staging was pT1 & pT2 only i.e. early stage. CK7 positivity was found in 91.6% cases and CK20 was positive in 16.7% cases. Both CK7 & CK20 was positive in 16.7% and both CK7 & CK20 was negative in one case (8.33%). Conclusions: Although the most common gall bladder histopathology diagnosis is chronic cholecystitis, the possibility of any incidental malignancy needs to be ruled out by mandatory routine histopathological examination of all cholecystectomy specimens.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

The comparative impact of histologic variants and grade has not been well described. Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

Role of immunotherapy in stage IV non-small cell lung cancer with liver metastasis: A NCDB analysis.

9046 Background: Despite approvals of immune checkpoint inhibitors in stage IV non-small cell lung cancer (NSCLC), survival benefit of immunotherapy (IO) in those with liver metastasis is controversial. Randomized controlled trials demonstrated conflicting results. Methods: Using National Cancer Database (NCDB), Stage IV NSCLC cases diagnosed in 2016-2017 with at least 30-day follow up were analyzed. Clinical demographics included age (20-69 vs. 70+), sex (male vs. female), race (whites vs. others), institution (academic vs. others), Charlson-Deyo score (0-1 vs. 2-3), year of diagnosis (2016 vs. 2017), Histology (adenocarcinoma NOS vs. other), brain metastasis (Yes vs. No), bone metastasis (Yes vs. No), liver metastasis (Yes vs. No). They were divided into liver-metastasis positive (LM+) vs. negative (LM-). Information regarding cancer treatment was limited to the first course of therapy, including surgery for primary lesion (Yes vs. No), radiation (Yes vs. No), multi-agent chemotherapy (Yes vs. No), and IO (Yes vs. No). Overall Survival (OS) analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analyses. A two-sided p-value &lt; 0.05 was considered as significant. Results: A total of 13,594 LM+ and 69,885 LM- cases met eligibility and further analyzed. 2,944 and 15,553 patients were treated with IO, respectively. No significant association between use of IO and status of liver metastasis was observed (p = 0.124). The median OS in LM+ cases was significantly shorter than that in LM- cases (5.0 vs 8.8 months, respectively, p &lt; 0.0001). Use of IO was associated with improved OS in both LM+ and LM- cohorts with similar HRs/p-values (0.62/ &lt; 0.0001 and 0.64/ &lt; 0.0001, respectively). Multivariate analysis demonstrated that use of IO had a significantly improved OS in both LM+ (HR = 0.69, p &lt; 0.0001) and LM- (HR = 0.64, p &lt; 0.0001) cohorts. The OS benefit of IO in LM+ cohort remained with propensity score matching analysis (mOS 9.0 vs. 4.4 months, HR = 0.62, p &lt; 0.0001). Further exploratory analysis focusing on those treated with multiagent chemotherapy showed that the addition of IO improved OS in both LM+ (HR = 0.77, p &lt; 0.0001) and LM- (HR = 0.79, p &lt; 0.0001) cohorts. Conclusions: This retrospective study using one of the largest cancer databases suggests that use of IO improves OS of NSCLC patients with LM regardless of chemotherapy status, and its magnitude of OS benefit is similar to that in LM- patients. [Table: see text]

Darolutamide for patients with androgen receptor positive salivary gland cancers (DISCOVARY): The results of phase 2 study of darolutamide monotherapy.

6093 Background: There is no standard first-line treatment for recurrent/metastatic (R/M) or unresectable locally advanced (LA) salivary gland cancer (SGC). Androgen receptor (AR) overexpression is known to be particularly high (43-92%) in SDC, depending on histology, and has been identified as a potential molecular target for SGC treatment. However, the clinical utility of this approach has not been well investigated. Here, we evaluated the efficacy and safety of darolutamide for patients with AR-positive SGC. Methods: Eligibility included LA or R/M, SGC histologically confirmed positive for AR by the central laboratory; PS 0-1; adequate organ function; and no suitable local therapy. The study consists of two sequential components: a monotherapy part with darolutamide alone (monotherapy part) and a combination part with darolutamide and goserelin (combination part). Darolutamide was given orally at 1,200 mg daily until disease progression or unacceptable toxicity. Primary endpoint for the monotherapy part was overall response rate (ORR) as determined by the investigator. Secondary endpoints were ORR by independent central review (ICR), clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. (ClinicalTrials.gov NCT05694819). Results: From Mar 2020 to Jan 2021, 24 patients were enrolled in the monotherapy component. Median age was 64.6 years and 23 were male. ECOG PS was 0/1 in 18/6 cases. Pathological diagnosis was salivary duct carcinoma, adenocarcinoma NOS, and carcinoma ex pleomorphic adenoma in 16, 4 and 4 patients, respectively. ORR by investigator was 8.3% (90% CI 1.5–24.0) and ORR by ICR was 20.8% (95% CI 7.1–42.2). CBR and DCR were 41.7% (95% CI 22.1–63.4) and 58.3% (95% CI 36.6–77.9), respectably. Median PFS and OS were 5.7 months (95% CI, 1.9–15.2) and not reached (95% CI, 15.5–not estimable [NE]), respectively, with a median follow-up period of 19.1 months. Nine patients (37.5%) had grade 3 or 4 treatment-related adverse events. There were no treatment-related fatal adverse events. Conclusions: This is the first prospective trial of darolutamide for AR-positive SGC. The response rate by ICR and other secondary endpoints confirmed clinically meaningful activity and a well-tolerated safety profile. Patient enrollment to the combination component is now ongoing to evaluate additional benefits. Clinical trial information: NCT05694819 .

Systemic therapy for salivary gland carcinoma

Systemic therapy for salivary gland carcinoma (SGC) is indicated for recurrent and/or metastatic (RM) disease. The background, goals of therapy, organ function, symptomatic or a symptomatic, and histopathology should be considered in each case. Adenoid cystic carcinoma with only lung metastasis often progresses slowly and many cases are followed up without therapy, whereas salivary duct carcinoma, adenocarcinoma NOS, or adenoid cystic carcinoma with multiple metastases, including lung, liver, and bone, often require the early introduction of systemic therapy.

Abstract 1014: High tumor mutational burden in patients with mismatch repair proficient metastatic colorectal cancer: Single institution cohort

Abstract Background: High Tumor Mutational Burden (TMB) in metastatic colorectal cancer (mCRC) is mostly associated to microsatellite instability (MSS/MMRp) or alterations in POLE/POLD1 genes [1]. Tumors harboring these molecular profiles are also associated with specific clinical-pathological features well described in literature [2; 3] and treatment with immune checkpoint inhibitors (ICI) represent the therapy with the highest expected benefit [4; 5; 6; 7; 8]. This subgroup of population represents almost 5% of the entire population of mCRC patients (pts) [9; 10]. About the remaining 95% of the population, for which immunotherapy doesn’t seem to improve outcome [4; 10; 11; 12], we know that a subgroup of pts reported high TMB, not related to MSS/MMRp or mutation in Polymerase genes [1]. For this subgroup data are scarce in the literature. Methods: We selected a case series of MSS/MMRp, non-POLE/POLD1 mCRC cases with documented TMB &amp;gt;= 10mut/Mb at comprehensive genomic profiling tested with Foundation Medicine panel between January 2019 and June 2022. Clinical-pathological features were collected from clinical reports and evaluated with descriptive statistics. Two pathologists reviewed the slides to assess histopathological features. Results: 24 out of 693 (3.5%) pts had MSS/MMRp, non-POLE/POLD1 mCRC with TMB &amp;gt;= 10 Mut/Mb. Average TMB was 19.04 mut/Mb (10 - 104.65 mut/Mb). 56% were male; median age at mCRC diagnosis was 58 years old (IQR 48-64 yo). 16 pts had left-side primary tumor, 6 of which had rectal cancer. 14 had synchronous metastases and the most frequent stage parameters were T3/4 and N+. The following histotypes were documented: 18/24 were adenocarcinoma NOS, 3/24 mucinous, 1/24 of cribriform comedonecrosis type, 1/24 a mixed neuroendocrine-non-neuroendocrine neoplasm (MiNen) and 1/24 not assessable. With regard to grading, 12/24 high-grade cases and 11/24 low-grade cases, 1 case not assessable. 7/18 assessable cases had high tumor infiltrating lymphocytes (TILs) (&amp;gt;=2.0 TILs/HPF) and 18/18 assessable cases showed signs of lympho-vascular invasion. According to comprehensive molecular profiling, the 5 most frequent genes altered were APC (80.0%), TP53 (72.0%), KRAS (24.0%), SMAD2/4 (24.0%), PIK3CA (24.0%). 3 pts had BRAF V600E mutations. In our case study, 23 out of 24 pts started 1st line treatment for metastatic disease, of which 21 with poli-chemo schedules. Data about best response were available for 21 cases and ORR was 61.9%, DCR 90.4%. Median PFS was 13.6 months (IQR 5.6 - 25.9). Median OS was 47.2 months (IQR 25.7 - 63.3). Conclusion: MSS/MMRp, non-POLE/POLD1, TMB &amp;gt;= 10 mut/Mb is a small but defined subgroup of mCRCs. To better understand the molecular behavior of this rare subgroup of cancers, further study should investigate the underlying mechanism, the TMB cut-off relevance in mCRC and the potential predictive impact on immunotherapy efficacy. Citation Format: Giulia Maddalena, Valentina Angerilli, Gianmarco Ricagno, Aldo Montagna, Riccardo Cerantola, Giada Munari, Sara Lonardi, Francesca Bergamo, Matteo Fassan. High tumor mutational burden in patients with mismatch repair proficient metastatic colorectal cancer: Single institution cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1014.

A 10-Year Review of Intraoral Salivary Gland Tumor Diagnoses: Diagnostic Challenges and Inter-Observer Agreement.

Salivary gland tumors (SGT) are a diverse group of neoplasms arising from the major and minor glands. The oral cavity is the most common site for minor SGT (IMSGT), and these lesions frequently pose a challenge to the pathologist due to overlapping histopathological features and limited material for analysis. Our objective was to determine specific clinical and histopathological features associated with challenges in IMSGT diagnoses and pathologists' agreement. We conducted a retrospective analysis of 248 IMSGT received between 2010 and 2019. We evaluated the diagnostic challenge of the cases by stratifying according to whether a definitive, favored, or indeterminate (challenging) diagnosis was provided. Inter-observer agreement and concordance of biopsy diagnoses with the final diagnoses after tumor resection were evaluated. Of the 248 biopsies, 191 had a definitive diagnosis, 38 favored diagnoses, and 19 were indeterminate. The predominant diagnoses considered for the indeterminate category were pleomorphic adenoma/myoepithelioma (PA), polymorphous adenocarcinoma (PAC), adenoid cystic carcinoma (AdCC), and low-grade adenocarcinoma. Using multivariate analysis of clinical features, younger patient age, smaller tumor size, and larger biopsy size increased the likelihood of a definitive diagnosis (p = 0.014, p = 0.037, p = 0.012). The inter-observer agreement for 68 representative cases was moderate overall (Fleiss's Kappa 0.575) and good for the 40 cases with a definitive diagnosis (Fleiss's Kappa 0.66). Sixty-five biopsy diagnoses were matched with corresponding tumor resection diagnoses and found to show a good concordance (Cramer's V test 0.76). The discordant diagnoses predominantly involved PA, carcinoma exPA, PAC, AdCC, and adenocarcinoma NOS. Diagnostic challenges in IMSGT incisional biopsies were infrequent, especially if multiple pathologists were consulted. PA, PAC, AdCC, and adenocarcinoma NOS were the histologic types more commonly posing diagnostic challenges. Younger patient age, smaller tumor size, and larger biopsy are associated with a definitive diagnosis. This data highlights the importance of appropriate sampling in IMSGT.

Surgical and Survival Outcomes of Operable Gastric Cancer-Experience from a Tertiary Care Center in South India.

Gastric cancer is one of the leading cancers in Southern India. Data regarding the gastric cancers among the Indian population is sparse. Most patients in our country have locally advanced gastric cancers due to delayed presentation. In this article, we present our data regarding the presentation patterns, epidemiological demographics, surgical outcomes, and survival patterns from a tertiary care center in South India. This is a retrospective analysis of gastric cancer patients who underwent gastrectomy in our institution between January 2015 and November 2021 (n = 102). The data regarding patient characteristics, histopathology, and perioperative outcomes were analysed from medical records. The adjuvant treatment received and survival details were collected from the follow-up records and by telephonic interviews. A total of 128 patients were assessable, 102 patients underwent gastrectomy in a period of 6years. The median age of presentation was 60years and males were more commonly affected (70.6%). Most common presentation was pain abdomen followed by gastric outlet obstruction. Adenocarcinoma NOS (93%) was the most common histological type. Most of the Patients had antropyloric growths (79.4%) and subtotal gastrectomy with D2 lymphadenectomy was the most common surgery performed. Majority of the tumors were T4 tumors (55.9%) and nodal metastases were detected in 74% of the specimens. Predominant morbidity was wound infection (6.1%) followed by anastomotic leak (5.9%) with a combined overall morbidity of 16.7% and 30-day mortality of 2.9%. Seventy five (80.5%) patients were able to complete all planned 6 cycles of adjuvant chemotherapy. The median time of survival calculated by Kaplan-Meier method was 23months with 2-year and 3-year overall survival rates of 31% and 22%, respectively. Lymphovascular invasion (LVSI) and lymph nodal burden were the risk factors associated with recurrences and deaths. The patient characteristics, histological factors, and perioperative outcomes revealed most of our patients presented in locally advanced stages with poor risk histological types and increased nodal burden contributing to the lower survival in our population. Inferior survival outcomes suggest the need to explore perioperative and neoadjuvant chemotherapy options in our population.

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

Activity of combination trametinib/navitoclax in patients with RAS-mutated gynecologic (GYN) cancers in a Phase 1/2 study (LBA 12)

<b>Objectives:</b> Preclinical data suggest that concurrent MEK and BCLxL inhibition can be synergistic. Mechanistically, inhibition of RAS signaling upregulates BIM, "priming" cells for apoptosis with BCLxL inhibition. A Phase 1 trial of the MEK inhibitor trametinib with the BCLxL inhibitor navitoclax was conducted to establish the recommended phase 2 dose (RP2D) and activity in select <i>RAS</i>-mutated tumors. We report the activity of this combination in patients (pts) with <i>RAS</i>-mutated GYN cancers. <b>Methods:</b> Pts with <i>RAS</i>-mutated GYN cancers were enrolled at the Dana-Farber Cancer Institute and Massachusetts General Hospital. Pts had RECIST 1.1 measurable disease and had progressed after at least one prior line of systemic chemotherapy. Eligible pts had cancers with activating mutations affecting codons 12, 13, 61, or 146 in <i>KRAS</i> or <i>NRAS</i>. Pts received combination trametinib and navitoclax either in dose escalation (7 pts) or in a dose expansion (24 pts) at the RP2D of navitoclax 250mg days 1-28 and trametinib 2mg days 1-14, following a lead-in cycle of navitoclax 150mg days 1-7 and 250mg days 8-28 with trametinib 2mg days 1-14 in 28-day cycles. <b>Results:</b> Between 1-22-2015 and 9-21-2021, 31 pts with GYN cancers (15 ovarian, 10 endometrial, 5 cervical, 1 mullerian) were enrolled. Data cutoff was 11-1-2021. Median follow-up is 4.9 mos. The median number of prior lines was 3 (range 1-7). Overall, 6 pts (19.4%; CI 7.5-37.5%) had a confirmed response. These included 3 ovarian cancers (1 low grade serous, 1 mucinous, 1 endometrioid), 1 endometrial (adenocarcinoma NOS), 1 cervical (mixed adenocarcinoma and neuroendocrine tumor), and 1 mullerian cancer (endometrioid). 9 pts stopped treatment before their disease was re-evaluated, and 1 pt's post baseline scan was deemed nonevaluable. Among 21 pts with at least one evaluable restaging scan, the response rate was 28.6% (95% CI 11.3-52.2%). Figure 1 shows the waterfall plot of best responses in these 21 pts. Median PFS time was 3.9 mos (95% CI 3.7-13.4) and 6-mo PFS was 37.7% (95% CI 17.5-57.9). In the 6 pts with response, the median duration for response was 9.5 mos (range 3.9-27.6). The most frequently observed adverse events included LFT changes, thrombocytopenia, diarrhea, nausea, and rash. <b>Conclusions:</b> Combined MEK and BCLxL inhibition with trametinib and navitoclax had clinical activity in pts with <i>RAS</i>-mutated GYN cancers, with a response rate in all pts of 19.4%. Among pts with at least one evaluable reassessment, the response rate was 28.6%. Further studies of combined MEK and BCLxL inhibition in pts with RAS-activated GYN cancers are warranted.Fig. 1

A Clinicopathological study of salivary gland neoplasms in a tertiary care hospital: A three year study

Background: The tumors of the salivary glands are uncommon head and neck neoplasms. The aim of this study was to observe the clinical occurrence of salivary gland neoplasms and to study the various histo-morphological features of salivary gland tumours, their frequency, age and sex distribution. Materials and Methods: The cases which have arrived to the Dental OP at Drs Sudha and Nageswara Rao Sidhhartha Institute of Dental Sciences with swellings in the head and neck region were identified and sent to pathology department from June 2013 to May 2016 and cases which were diagnosed as salivary gland neoplasms (96 cases) were taken into consideration and Histopathological examination was done. Results: Out of 96 cases, 51 (53.1 %) were benign and 45(46.9 %) were malignant with M:F ratio of 1.74:1. Age range of patients was from 10 to 80 years. Pleomorphic adenoma was found to be the commonest benign tumor (74.5 %), followed by Warthin’s tumor (19.6%), monomorphic adenoma (3.9 %) and basal cell adenoma (3.9 %). The mucoepidermoid carcinoma was the most common malignant tumor (48.8%) followed by adenoid cystic carcinoma (33.3%), acinic cell carcinoma (13.3%), adenocarcinoma NOS (2.2%) polymorphous adenocarcinoma (2.2%) Conclusion: Males were more affected than females and pleomorphic adenoma was the most frequent lesion followed by warthin’s tumor among benign neoplasms. Mucoepidermoid carcinoma is the most common malignant neoplasm followed by adenoid cystic carcinoma.

HER 2 in Gastric Cancer in Albania as a New Therapeutic Alternative

Background: Gastric cancer (GC) is the fourth most common cancer in Albania. Gastric cancer has a 5-year survival rate as low as 30%. The expression of HER2 in gastric cancer has brought a new alternative treatment for patients. Materials and method: 192 patients were analyzed retrospectively, with primary GCs for HER2 overexpression by IHC and Dual SISH in equivocal cases. This was compared with the results of HER2 in gastric patients in surgical specimens and endoscopic biopsies and there is a correlation between gender, age, stage, and type of the histopathologic gastric cancer diagnosis. Results: Examinations were made by immunohistochemistry for HER2 in 73.4% (141 cases) of surgical specimens and 26.5% of endoscopic biopsies: 18.4% (26 cases) and 15.7% (8 cases) were HER2 3+, respectively. HER2 overexpression (3+) was detected in 17.7% (34 cases). HER2 Equivocal (2+) was detected in 24.5% (47 cases). 17.8%, 14%, and 4.7% were respectively intestinal type, diffuse, signet ring, and the rest adenocarcinoma NOS. GC prevailed in the group aged 61-70 yrs. (31.70%), followed by 51-60 yrs. (25%), 22.9% in 71-80-yrs. 20 cases analyzed by SISH, showed HER2 amplification in 40% (8cases). Economical restrictions and problems with the preanalytical phase made it impossible to evaluate by SISH all 20 cases. Conclusion: 17.7% of Albanian patients with primary GC were HER2-positive on IHC. There is no difference in biopsy and surgical specimen results. Economic restrictions can influence the results.

Abstract 2770: Microbiota, mutational landscape and tumor sidedness of colorrectal cancer

Abstract Background: Colorectal cancer (CRC) is one of the most common cancers in the world, and it is one of the leading causes of cancer-related death. New biomarker candidates have emerged as an important prognostic and predictive factor and genetic profile approach has been used in the choice of targeted therapies and in the prediction of drug response. The aim of this study was performed a comprehensive genomic profile and intestinal microbiota characterization in peruvian CRC patients to define biomarkers for decision making. Methods: Patients with CRC diagnosed in 2019 and treated at INEN were included. Tumor samples were collected to assessed the presence of high-risk human papillomavirus (HPV) and Epstein-Bar virus (EBV) by qPCR, microsatellite instability (MSI) by IHC and somatic genomic alterations by next generation sequencing (NGS) using Ampliseq FOCUS panel (Illumina). Fecal samples were self-collected to performed V3-V4 region 16S ribosomal RNA metagenomics sequencing (Illumina). Results: The study included 40 CRC patients with a mean age at diagnosis of 56 (28-90) years, 59.2% were men. Clinical stages were distributed, in I-II (16.5%), III (37.5%), IV (27.5%). The remaining 12.5% had an unknown tumor stage at diagnosis. The 62.5% of patients underwent tumor surgical treatment. Most tumors (85%) were adenocarcinoma NOS and moderately differentiated (65%). Tumor location was rectum (RC; 27.5%), right side colon (RCC; 42.5%) and left side colon (LCC; 30%). Chemotherapy was administered in 30%. The median follow-up period was 11.1 months (2-28). MSI was high (20%), low (10%) and stable (70%). HPV and EBV DNA was detected in 42.5% and 82.5% of CRC patients respectively. The prevalence of genomic alterations was 77.5%. KRAS alterations were found in 47.5% patients. BRAF (5%), NRAS (2.5%), PIK3CA (12.5%), APC (2.5%), and AKT1 (2.5%). All PIK3CA and BRAF variants were found in RCC. No variants were found in the NTRK or HER2 amplifications. Patients with BRAF variant had a median survival rate only 5 months (3-7). MSI-high/low was present only in colon, showing dominance on the RCC (66.7%). Verrucomicrobia, Staphylococcus, Peptostreptococcus and Clostridium were present in both RCC and LCC. Clostridium and Peptostreptococcus were highly enriched in the LCC. Campylobacter and Spirochaeta were found only in the LCC. Surprisingly, Fusobacterium was found in RCC except one patient in LCC. Bifidobacterium and Acinetobacter were present only in LCC and RC. Elusimicrobia, Shigella and WPS-2 were found only in RC. Conclusion: The current pressure to select the best treatment has generated intense interest in the evaluation of CRC molecular alterations characteristic to define prognostic and predictive biomarkers of disease and treatment in our population. This study constitutes the first integrative biomarkers research in peruvian CRC patients showing a diferent molecular signatures between RCC, LCC and RC patients. Citation Format: Bruno A. Muñante Luna, Jhoysi Casas Goñas, Manuel Chumpitaz, Juan Pablo Cerapio, Marcos Santos Chavez, Mariela Huerta-Rosario, Franco Doimi Garcia, Juan F. Olivos Gonzales, Claudia Jiménez Orosco, Daniel Valdivia Leonardo, Luis F. Barreda Bolaños, Silvia Neciosup Delgado, Victor Castro Oliden, Paola Montenegro Beltran, Luis Mas Lopez, Eduardo Payet Meza, Carolina Belmar-López. Microbiota, mutational landscape and tumor sidedness of colorrectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2770.

Comparison of tumor registry reporting and gastrointestinal oncologist determination of intrahepatic cholangiocarcinomas: A quality review analysis.

e16113 Background: Diagnosing cholangiocarcinoma (CCA) can be challenging and these tumors are often misclassified as adenocarcinomas of unknown primary (AUP). Accurate identification is critically important to determine the true incidence and to understand the epidemiology of these cancers. Methods: As a quality assessment, gastrointestinal oncologists at our institution reviewed the tumor registry records of all patients diagnosed with intrahepatic CCA, extrahepatic CCA, hepatocellular carcinoma, adenocarcinoma of unknown primary, and adenocarcinoma not otherwise specified. Mixed hepatocellular/cholangiocarcinoma was excluded. Results: Initially the tumor registry reported 37 cases of intrahepatic CCA at the Lifespan Cancer Institute/Rhode Island Hospital between 2017-2020. However, review of the registry records by gastrointestinal oncologists revealed 10 additional cases of intrahepatic cholangiocarcinoma. These cases had been entered into the tumor registry with diagnosis codes of liver adenocarcinoma NOS (n = 8), liver cancer (n = 1) and liver NOS (n = 1). Following review, a total of 47 cases of intrahepatic CCA and 59 cases of extrahepatic CCA were identified at our institution between 2017-2020. The mean age of intrahepatic CCA was 58 and 48% were women. The mean age of extrahepatic CCA was 73 and 42% were women. The updated numbers were reported to the state tumor registry. Conclusions: Difficulties in diagnosis of cholangiocarcinoma may underestimate the true incidence of this disease in the United States. Careful review of tumor registry data across the United States would likely reveal large discrepancies between actual and reported incidence of this disease and further study is warranted.

IDENTIFICATION OF SECRETORY CARCINOMA IN ARCHIVAL MATERIAL BY HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL METHODS WITH MOLECULAR PROFILING OF ETV6 AND RET ON ALTERNATIVELY DIAGNOSED SALIVARY GLAND TUMORS

<h3>Introduction</h3> Secretory carcinomas (SC) of minor and major salivary gland (SG) are rare neoplasms that demonstrate microscopic overlap with acinic cell carcinomas (ACC), adenocarcinoma NOS (AdNOS), and mucoepidermoid carcinomas (MEC) respectively. Recently alternative translocations of ETV6-RET gene locus have been recognized in a small group of SC. This study aims to identify previously undiagnosed SC, from the archival cases of tumors signed out as other salivary malignancies and identify the novel ETV6 and RET genes by Fluorescence in situ hybridization (FISH). <h3>Materials and Methods</h3> We performed a retrospective search of ACC, AdNOS and MEC within the annals of the UF, Oral Pathology Biopsy service from 2000-2020. Inclusion criterion using histopathological characteristics of SC were created. A total of 205 cases encompassing ACC, AdNOS and MEC were retrieved. All cases were screened with established histologic criteria and were stained (IHC) with S100 and mammaglobin. FISH was performed on one case with sufficient tissue for testing to evaluate the presence of ETV6-RET fusion. <h3>Results</h3> Ten out of 205 cases met the histologic inclusion criteria. Five out of these ten cases were positive for S100 and mammaglobin confirming the diagnosis of SC. These cases were previously diagnosed as AdNOS (n=2), ACC (n=2) and MEC (n=1) respectively. Most of the SC in this series were seen around the 5^th decade (mean age = 55.4) and demonstrated a slight male predilection. (71.4%). Buccal mucosa was the most affected site (60%), followed by hard palate and soft palate (40%). A single break apart probe of both ETV6 translocation and chromosomal deletion of RET was established in the tested case. <h3>Conclusion</h3> SC is a recently accepted salivary gland neoplasm. Our study strengthens the understanding of this entity by assessing the histopathological features of SC and identifying a new subset of ETV6 and RET genes.

First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer

BackgroundAdvanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.MethodsThis study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.ResultsSix patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.ConclusionsPalliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases

PurposeSalivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy.MethodsMonocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan–Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis).ResultsThe median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards.ConclusionWith surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.