Mucinous Carcinoma Research Articles

Poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas in a 17-year-old female patient: a case report

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and screening colonoscopy has led to a decreasing incidence rate. However, the incidence of CRC is increasing among young people, especially adolescents and young adults (AYAs) who are not routinely screened. Although CRC is the fourth most common cancer among AYAs, it is extremely rare. In younger patients, CRC is often diagnosed later, and the proportion of patients with advanced CRC is higher than that in older patients. We herein present a case of poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas (MCTs) in an AYA.Case presentationA 17-year-old female patient presented with a chief complaint of abdominal pain and diarrhea that had persisted for more than 3 years. Colonoscopy revealed circumferential wall thickening of the ascending colon, and colonic biopsy revealed a mucous mass and findings of adenocarcinoma, predominantly signet ring cell carcinoma. Abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) showed bilateral ovarian tumors. Laparoscopic right hemicolectomy and enucleation of bilateral ovarian tumors were performed. Although the ascending colon cancer formed a large mass, there were no signs of peritoneal dissemination or direct invasion to the surrounding organs. Microscopically, the ascending colon was a poorly differentiated mucinous carcinoma with signet ring cell carcinoma and lymph node metastasis (9/42). The ovarian tumors were diagnosed as MCTs without any malignant components. The pathological diagnosis was ascending colon cancer (pT4aN2bM0, pStage IIIC) and bilateral ovarian MCTs. Microsatellite instability (MSI) testing was negative, and there were no gene mutations in either RAS or BRAF. Postoperative adjuvant chemotherapy with oxaliplatin and 5-FU was started.ConclusionsWe presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

Primary cutaneous mucinous carcinoma in a periorbital lesion: two case reports and literature review.

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignancy of the sweat glands that most commonly affects the periorbital area. It is characterized by slow growth over a prolonged period, and its morphology can be easily confused with a benign tumor, such as an epidermal cyst. Consequently, many patients experience recurrence after undergoing multiple resections. However, there are few reports concerning the surgical management of PCMC. We present two cases of PCMC originating in the periorbital area. The first case involved a 76-year-old man with a mass measuring 3.0× 1.5 cm that had been increasing in size. The second case was a 61-year-old man with two masses, each measuring 1.0× 1.0 cm, that were also growing. Both patients underwent wide excision with a 5-mm safety margin, which was determined based on the widest view of the cross-section of the mass on the magnetic resonance imaging. Subsequently, based on the intraoperative frozen biopsy results, both patients underwent additional excision with a 5-mm safety margin in only one direction. This report shows that, when determining the surgical margin of PCMC in periorbital area, employing imaging modalities and intraoperative frozen biopsies can be helpful for narrowing the surgical margin.

Peak Resembling N-acetylaspartate (NAA) on Magnetic Resonance Spectroscopy of Brain Metastases.

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the "NAA-like peak", was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.

A Cross-Sectional Study of Tumor Budding in Correlation with Clinicopathological Parameters in Invasive Breast Carcinoma

Introduction: Breast carcinoma is the largest cause of mortality from cancer among women in India. Tumor budding is usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumor front. Tumor budding is associated with poor clinicopathological characteristics, such as Tumor size, tumor differentiation, lymph node invasion, lymphatic or vascular invasion etc. Aim: To study tumor budding and its association with known clinicopathological parameters and hormone receptor status in invasive breast carcinoma. Methods : A Cross-sectional study was conducted after approval from the ethics committee. The duration of study was 1.5 years (Jan 2022- June 2023). Results: A total of fifty cases of invasive breast carcinomas were included in this study. 70% (35cases) were >50yrs of age, 65% (33cases) were of T2 (tumor size) category. 82%(41cases) of Invasive duct carcinoma, No specific type, 12% (6 cases) of mixed carcinomas followed by three cases, one is invasive lobular carcinoma(6%), others are high grade papillary duct carcinoma(6%) and mucinous carcinoma (6%). 76%(38cases) showed presence of lymphovascular invasion, 74%(37cases) showed absence of necrosis, 54%(27 cases) are categorized as grade 2. High grade tumor budding was seen in 54% (27 cases). Conclusion: The following variables had a significant association with the tumor budding in present study: Tumor size, TNM staging, treatment status, lymphovascular invasion showing a p-value of <0.05. ER positive tumors are also associated with high grade tumor budding. Keywords: Breast Carcinoma, Clinicopathological Variables, Lymphovascular Invasion, Tumor Budding

Spectrum of Special Variants of Breast Carcinoma and Differentiated Ductal Carcinomas with their Immunohistochemistry Profile in a Tertiary Care Centre

Background: Breast cancer is a diverse disease with varying characteristics in morphology, presentation, treatment, and prognosis. It constitutes 25% of cancers in Indian women. This study delves into rare special variants and differentiated ductal carcinomas, focusing on their unique histological features and molecular profiles. Aim: To scrutinize the spectrum of special forms of breast carcinoma and their immunohistochemistry (IHC) profile. Material and methods: A retrospective analysis of all the breast carcinomas over a period of 11 months was carried out. The clinical, gross, microscopic and immunohistochemistry findings of 15 special variants and differentiated ductal carcinomas were noted down. Results: In a retrospective analysis of 50 cases of breast carcinoma, 15 were diagnosed as special variants of breast malignancy which accounted to be 30%. Out of the 21 rare histologic subtypes of breast carcinoma 10 variants were encountered by us that included mucinous carcinoma, lobular carcinoma, papillary carcinoma, invasive breast carcinoma with medullary pattern, invasive breast carcinoma with oncocytic pattern, metaplastic carcinoma, cribriform carcinoma, malignant adenomyoepithelioma, secretory carcinoma, and invasive breast carcinoma with neuroendocrine differentiation. Conclusion: This study provides a comprehensive overview of the gross and microscopic features, as well as the immunohistochemistry profiles of these special variants and differentiated ductal carcinomas of the breast. We anticipate that this research will enhance our understanding of these uncommon breast cancer variants, with a particular emphasis on their molecular characteristics, contributing to improved management strategies in the future. Keywords: Breast Cancer, Immunohistochemistry, Molecular Classification

Structural Elucidation and Prognostic Relevance of 297-11A-Sulfated Glycans in Ovarian Carcinoma

Ovarian carcinoma is usually diagnosed at an advanced stage with peritoneal dissemination and/or lymph node metastasis, and the prognosis for such advanced carcinoma is very poor. Therefore, new biomarkers to predict patient prognosis are needed. Miyamoto et al. previously showed that keratan sulfate (KS) detected by the 5D4 monoclonal antibody was expressed in ovarian carcinoma. However, the detailed structure of such KS was not determined, and the biological significance of this finding remained to be clarified. We previously generated the 297-11A monoclonal antibody, which recognizes galactose (Gal)-6-O-sulfated N-acetyllactosamine (LacNAc) located at the nonreducing terminus. Because the 297-11A epitope overlaps with that of 5D4, here we chose to use the 297-11A antibody as a tool to analyze KS and related structures. We conducted immunohistochemical analysis of 98 ovarian carcinoma cases with 297-11A antibody combined with a series of glycosidases and performed mass spectrometry analysis of the human serous ovarian carcinoma cell line OVCAR-3 to deduce the glycan structure of 297-11A-sulfated glycans. We also performed western blot analysis to assess a potential association of 297-11A-sulfated glycans with the mucin core protein mucin 16 (MUC16; also known as cancer antigen 125 (CA125)). Finally, we examined the relationship between 297-11A expression and patient prognosis. Consequently, 297-11A-sulfated glycans were primarily expressed in serous and endometrioid carcinomas and poorly expressed in mucinous and clear cell carcinomas. We reveal that structurally, 297-11A-sulfated glycans expressed in ovarian carcinoma are O-glycans carrying partially sialylated, Gal-6-O-sulfated LacNAc and that these glycans are likely displayed on MUC16 mucin core proteins. Of clinical importance is that expression of 297-11A-sulfated glycans correlated with shorter progression-free survival in patients. Thus, 297-11A-sulfated glycans may serve as a predictor of ovarian carcinoma recurrence.

Primary Mucinous Carcinoma of the Axillary Skin: A Case Report & The Role of Adjuvant Tamoxifen

Primary mucinous carcinoma of the skin (PMCS) is a rare cancer. It is indolent and progresses slowly but can recur locally, damaging the structure. The majority of mucinous carcinoma that occurs in the skin are metastatic lesions originating from various sites. In terms of morphology, PMCS is almost indistinguishable from secondary metastatic deposits. We reported a case of a 44-year-old male with left axillary skin PMCS that had spread to axillary lymph nodes. The pathologic diagnosis was challenging but was facilitated by expert pathologists from different centers. A multidisciplinary meeting concluded that the best managementapproach was to include a wide local excision and axillary clearance followed by adjuvant tamoxifen. The role of adjuvant radiotherapy was discussed but was declined by the patient. The patient is well now with no recurrence, 22 months since the diagnosis.

Abstract 4685: The identification of new therapeutic targets in mucinous ovarian carcinoma

Abstract Background: Epithelial ovarian cancer (EOC) is the second cause of death among gynaecological cancersworldwide. Mucinous ovarian carcinoma (mEOC) accounts for 3-5% of all EOCs, and when diagnosed at anadvanced stage its prognosis is very poor mainly for its limited chemosensitivity. PLK1 is a member of thewell-conserved serine/threonine kinase family, that plays a key role in the progression of mitosis, in the G2/Mcheckpoint regulation, DNA damage replication, stress response, and cell death pathways. mEOC has beenshown to be sensitive to PLK1 inhibition both with siRNA and small molecule inhibitor (onvansertib). Giventhis background and the need for new therapeutic approaches in mEOC, the purposes of this work were toidentify new therapeutic targets in mEOC using CRISPR/Cas9 lentivirus libraries and to find synthetic lethalpartners with the PLK1 inhibitor onvansertib. Methods: We used three different mucinous cell lines: MCAS,EFO27, TOV2414, overexpressing Cas9 gene. We evaluated the Cas9 expression through Western Blotanalysis, and the Cas9 activity through a Fluorescent Activated Cell Sorter- based-GFP assay. We used twodifferent lentiviral gRNAs Libraries (Bassik Library Human CRISPR Deletion Library - Apoptosis and cancer(Addgene #101926)/Drug targets, kinases, and phosphatases (Addgene #101927)). The EFO27 Cas9 cells wereused for the screening experiment. Cells were infected with the lentiviral libraries at MOI of 0.3 and put inpuromycin selection. Six days after puromycin addition (Time point 0) 30x10^6 cells were collected forsequencing. The remaining 30x10^6 cells were split in two: control cells and cells treated with a subtoxic doseof onvansertib (IC30). After 7 days (Time point 1) 30x10^6 cells for each condition were collected forsequencing. The infection of libraries was performed alone and in combination with sub-toxic onvansertibtreatment, to identify genes important for mucinous carcinoma cell survival, and those genes in syntheticlethality with onvansertib. Results: Bioinformatic analyses comparing control cells (time 1 vs time 0) andPLK1 treated and non -treated cells (time 1) allowed the generation of a gene ranking list, including genesinvolved in survival of EFO27 cells like ZC2HC1C, RPA2, POLE3, KIN, TUBG1, SMC2, CDC26, CDC42, HOXA9,TAF10, DCLRE1C, SENP1, MRPS31, COPS2; and genes in synthetic lethality with PLK1 treatment, like JUND,CARD9, BCL2L2. Validation experiments are ongoing and will be presented and discussed. Conclusion: Using a CRISPR-based approach, we identified genes that either alone or in combination with PLK inhibitioncould have therapeutic value in mEOC. Citation Format: Serena Petrella, Marika Colombo, Mirko Marabese, Chiara Grasselli, Andrea Panfili, Ilaria Craparotta, Maria Chiara Barbera, Giada Andrea Cassanmagnago, Marco Bolis, Giovanna Damia. The identification of new therapeutic targets in mucinous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4685.

Abstract 6102: Clinicopathological and genetics features of endometrial cancer in Algerian women: The first nation-wide study

Abstract Background: Endometrial cancer represents the fourth common cancer in women in Algeria and the fifth cause of cancer mortality. In the present study, we aimed to determine, clinical, tumor and genetics characteristics associated with endometrial cancer in Algerian women. In addition, we screened for germline pathogenic variants in MMR genes in endometrial cancer patients with strong family history of Lynch syndrome (LS). Materials and Methods: Our study population included 273 patients diagnosed with endometrial cancer between 2010 and 2021. Data were collected from three public hospitals that covered 29 provinces among 48 in Algeria. Patient and tumor information included: age at diagnosis, menopausal status, histological type, histological grade, TNM stage, FIGO stage, tumor markers CA125, ACE, CA19-9, family history with cancer and age at menarche . MLH1 (exons 1, 9, 10, 13, 16), MSH2 (exons 5, 6, 7, 12), MSH6 (exons 4 and 8) and PMS 2(exons 6 and 10) were screened by PCR-Sanger direct sequencing in 14 LS families . Results: The mean age at diagnosis was 58.88 years. The mean age at menarche was 13.5 years. The proportion of endometrial cancer patients with premenopausal status was 21.62%. The commonest histological type was endometrioid adenocarcinoma (66.79%) followed by clear cell carcinoma (8.10%), carcinosarcomas (3.86%), serous carcinoma (3.47%) and mucinous carcinoma (2.7%). We found that the proportion of tumors with histological grade I (34.74%), grade II (27.41%) and grade IV (21.40%) was commonest in 83.55% of the patients. Our results showed that 73.74% of the patients were diagnosed at stage I (50.19%), stage II (12.74%) and stage III (10.81%), respectively. For the FIGO staging, our results showed that 74.12% of the patients were diagnosed at stage I (52.89%), stage III (10.81%) and stage I (10.42%), respectively. 16.21%, 3.08%, 6.94% of the patients were positive for CA125, ACE and CA19-9, respectively. We noticed that 56 patients (20.43%) had a positive family history with HBOC syndrome (17), Lynch syndrome (26) and Cowden syndrome (13), respectively. We identified two distinct germline pathogenic variants in MLH1 gene in two LS families. We detected the new germline pathogenic variant MLH1 c.53_63delinsT in young patient diagnosed with endometrial cancer and colorectal cancer (CRC) at age 43y and 44 y, respectively. The rare pathogenic germline variant MLH1 c.1546C>T has been detected in young woman diagnosed with CRC at age 41y and endometrial and ovarian cancers at age 52y, respectively. Conclusions : In this first study, we reported some clinical, biological, tumor and genetics features of endometrial cancer in Algerian women. Interestingly, we noticed that the median age of diagnosis was younger that the average age in Europe and America. Genetic counseling and testing is recommended for endometrial cancer patients diagnosed before age 50 with a family history of Lynch syndrome. Citation Format: Farid Cherbal, Chiraz Mehemmai, Mouchira Saidi, Yasmine Santoudji, Djamel-Eddine Seddik, Asma-Lamia Boumehdi, Fatiha Gouaref, Kamel Bentabak, Hassen Mahfouf, Mohammed Oukkal. Clinicopathological and genetics features of endometrial cancer in Algerian women: The first nation-wide study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6102.

Abstract 3889: Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests

Abstract Objective: Comprehensive genomic profiling (CGP) tests were approved in Japan in June 2019 under universal health insurance coverage for cancer patients who have finished (or almost finished) standardized treatment. All the data are collected to the “Center for Cancer Genomics and Advanced Therapeutics (C-CAT)” under written informed consent. Up to date, over 60,000 CGP data have been deposited with a 99.7% consent rate. This study aims to analyze mutational landscape of gynecologic cancers, especially with poor prognosis, by using this database. Methods: We analyzed CGP datasets from 3,006 gynecologic cancer patients using FoundationOne® CDx (F1CDx), the most commonly tested in Japan. This study was ethically approved by our institutional ethics committee (#2021341G) and the Information Utilization Review Board of C-CAT (#CDU2022-026N). Results: Endometrial cancers (n=561) showed high rates of tumor mutational burden-high (TMB-H) (13.9%) and MSI-high (MSI-H) (10.8%), especially in endometrioid carcinomas. POLE exonuclease mutations were less frequent (1.4%) compared to TCGA data (7%), while TP53 mutations were more common (54.4% vs. 29% in TCGA), suggesting the impact of prognosis of the molecular subtypes. Other frequently mutated genes included PIK3CA (41%), PTEN (35%), ARID1A (31%) and KRAS (26%). In 839 cervical cancers, TMB-H prevalence was 14.2%, with low MSI-H at 1.5%. TMB-H was significantly higher in squamous cell carcinomas (20.6%) than adenocarcinomas (8.3%). Frequent mutations included PIK3CA (32%), STK11 (20%), TP53 (20%), KRAS (14%), and CDKN2A (11%). TP53 mutations were significantly higher than TCGA data (<5%), particularly in mucinous carcinomas (60%), indicating a prevalence of HPV-independent tumors with poorer prognosis. Actionable mutations were generally more frequent in adenocarcinomas than in squamous cell carcinomas, including KRAS (32.2%), TP53 (29.4%), CDKN2A (18.3%), and ERBB2 (16.7%). In 1,606 ovarian cancers, the ratio of TMB-H was 5.0%, and MSI-H was 1.2%. TMB-H rates varied between 3.3-6.5% across histological types, while the ratio of MSI-H was significantly lower in serous carcinomas (0.3%) than non-serous carcinomas. Pathogenic mutations in the POLE exonuclease domain were rare in cervical (0.0%) and ovarian (0.2%) cancers. Conclusion: The C-CAT database offers insights into the mutational landscape of various cancers and histological subtypes, especially those with poor prognosis, highlighting the unmet needs for drug development in these gynecologic cancers. Citation Format: Qian Xi, Hidenori Kage, Miho Ogawa, Asami Matsunaga, Akira Nishijima, Kenbun Sone, Kei Kawana, Katsutoshi Oda. Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3889.

Abstract 1041: Spatial concordance between genome and proteome in oncology: A systematic review

Abstract We recently reported that spatial transcriptome data can be used to spatially detect copy number alterations (Erickson et al., Nature, 2022). Given that copy-number alterations may also be reflected by altered protein expression in human cancers, we sought to determine what the empirical concordance of the spatial proteome and genome in human cancer samples. We performed a systematic review of Immunohistochemistry (IHC) & Fluorescence/Chromogenic In-Situ Hybridization (FISH/CISH) across human cancers. We performed a PUBMED query for records up to April 1st, 2023, yielding 9,294 records. Our inclusion criteria included human sample studies that performed both IHC and FISH/CISH against the same target, with a minimum of two samples. We excluded case reports, RNA ISH- and non-human studies, studies without IHC/ISH performed on the same target, and articles not in English or inaccessible. We screened 9,294 PUBMED article abstracts using the AS Review active learning model (van de Schoot et al., 2021), and used a pre-defined threshold of 5 % consecutive irrelevant abstracts to stop screening. A total of 1,309 abstracts were manually excluded using the AS Review, directing the active learning model to automatically exclude 3,413 abstracts out of the original 9,294. Of the 4,572 articles assessed for full-article screening, 1,167 were excluded for being out of scope, 303 for access issues, 227 for language incompatibility, and 236 for imprecise information, primarily due to non-representative samples or incorrect gene/protein target identification. Ultimately, out of 2,413 articles assessed for eligibility, 2,294 did not meet inclusion criteria, leaving 119 studies for our analysis. From these articles, we manually extracted kappa values for analysis and visualization in R. We identified articles from 19 different cancers with the majority studying Breast Cancer, Non-Small Cell Lung Cancer, Gastric Cancer, and Mesothelioma. We observed high Cohen’s Kappa values in Breast Cancer (median = 0.76), Non-Small Cell Lung Cancer (median = 0.91) and Mucinous Ovarian Carcinoma (median = 0.93). We identified studies from 14 different genes with majority being HER2, ALK and MYC. We observed high Cohen’s Kappa values in HER2 (median = 0.80), ALK (median = 0.80), ROS1 (median = 0.95) and MDM2 (median = 0.72). Our preliminary analysis indicates significant heterogeneity between tumor types for protein expression and copy-number alterations. To our knowledge, there are no previously reported systematic reviews that have empirically assessed the spatial concordance of proteome and genome, in human cancer samples. The authors often reported IHC/FISH results at patient, or section level, potentially introducing selection bias by not accounting for intra-tumoral heterogeneity at single-cell resolution. Future efforts are needed to spatially resolve gene-copy number and protein expression at single-cell resolution. Citation Format: Laura K. Sysivirta, Franziska Niemeyer, Veera Kurki, Inkalilja Pirinen, Laura Savolainen, Ceren Seref-Vujaklilja, Andrew Erickson. Spatial concordance between genome and proteome in oncology: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1041.

Abstract 1046: Prevalence of MTAP deficiencyin human cancer: A tissue microarray study on 17,078 cancers from 149 different tumor types

Abstract The S-methyl-5′-thioadenosine phosphorylase (MTAP) gene is located at 9p21 and is often co-deleted with CDKN2A. Because homozygous MTAP deletions result in a complete expression loss, MTAP immunohistochemistry (IHC) can be used for detection of homozygous deleted cells. MTAP IHC is of diagnostic utility for the distinction of mesotheliomas (often 9p21 deleted) from benign mesothelial proliferations. Moreover, evidence is emerging that MTAP deficiency results in a critical vulnerability of cancer cells towards drugs targeting several different pathways that depend on a functional MTAP gene and also causes resistance to immune checkpoint inhibitors. To determine the prevalence of complete MTAP expression loss and to assess the diagnostic utility of MTAP IHC, a tissue microarray containing 17,078 samples from 149 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by IHC. All cases with complete MTAP loss were validated by fluorescence in situ hybridization (FISH). In normal tissues, MTAP was ubiquitously expressed resulting in a cytoplasmic and nuclear MTAP staining. At least one case with a complete MTAP expression loss was observed in 87 of 149 (58%) tumor categories. MTAP staining was most commonly lost in neuroendocrine neoplasms of various sites (up to 80%), Hodgkin’s lymphoma (38%), mesothelioma (24-30%), bilio-pancreatic adenocarcinomas (9-36%), urothelial neoplasms (19-29%), malignant melanoma (14-21%), mucinous carcinoma of the ovary (27%), squamous cell carcinomas of various organs of origin (up to 24%), various types of sarcomas (up to 20%), adenocarcinoma of the lung (11%), gastro-esophageal adenocarcinomas (2.6-11%), and in various types of non-Hodgkin’s lymphomas (up to 14%). FISH validation identified homozygous 9p21 deletions in 90-98% of cases with MTAP expression loss in most tumor categories including urothelial neoplasms, mesotheliomas, and pancreatic cancers, and others. There were, however, also tumor types such as neuroendocrine tumors and Hodgkin’s lymphomas that always lacked 9p21 deletions. In summary, our data provide a comprehensive overview on MTAP expression in cancer and show a strong link between MTAP expression loss and homozygous 9p21 deletions in most tumor entities. These cancers might most benefit from cancer drugs targeting MTAP deficiency. The absence of 9p21 deletions in other entities with frequent MTAP expression loss demonstrates that other mechanisms can cause significant MTAP downregulation. Whether these tumors benefit from targeting MTAT deficiency remains to be determined. Citation Format: Natalia Gorbokon, Maximilian Lennartz, Doris Hoeflmayer, Sebastian Dwertmann Rico, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Christoph Fraune, Andreas M. Luebke, Claudia Hube-Magg, Franziska Büscheck, Anne Menz, Ria Schlichter, Till Krech, Andrea Hinsch, Eike Burandt, Guido Sauter, Ronald Simon, Stefan Steurer, Andreas H. Marx, Patrick Lebok, David Dum, Sarah Minner, Frank Jacobsen, Till S. Clauditz, Christian Bernreuther, Martina Kluth. Prevalence of MTAP deficiencyin human cancer: A tissue microarray study on 17,078 cancers from 149 different tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1046.

A Complex Case: Solid Unilateral Ovarian Mucinous Carcinoma Masquerading as Leiomyosarcoma in Postmenopausal Women

Introduction:: Ovarian cancers are the third most common gynecological and 8th most common cancer in women, associated with high mortality rates globally. Case Presentation:: A 60-year-old postmenopausal woman presented to the Gynecological outpatient department with complaints of pain in the abdomen for 2-3 months and loss of appetite with weight loss for 1-2 months. She was diagnosed as a case of uterine leiomyosarcoma or left adnexal mass on ultrasound and MRI. Intra-operatively, she was diagnosed with a unilateral left ovarian malignant mass, predominantly solid in consistency with metastasis to the left fallopian tube, uterus, cervical stroma, and omentum. The right ovary and tube were healthy. On histopathological examination, the final diagnosis of primary mucinous ovarian carcinoma was made. The patient tolerated staging laparotomy (total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy) well and was started on six cycles of adjuvant chemotherapy with Paclitaxel and Carboplatin injections along with Bevacizumab. Conclusion:: Primary mucinous ovarian carcinomas are rare and distinct subtypes of epithelial ovarian carcinomas. Due to their strong resemblance to other ovarian tumors and leiomyosarcoma, their diagnosis becomes challenging. Hence, it is crucial to consider leiomyosarcomas in the differential diagnosis of ovarian masses, especially in postmenopausal women.

Breast tissue imaging atlas using ultra-fast confocal microscopy to identify cancer lesions.

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images. One hundred sixty patients who underwent conserving surgery for breast cancer were included. Their fresh surgical specimens were sliced, stained with acridine orange, and imaged at high resolution with large-field-of-view UFCM. The resulting images were digitally false colored to resemble frozen sections. Each UFCM image was correlated with the corresponding definitive histology. Representative images of normal tissue, inflammation, benign lesions, invasive carcinoma (IC), and ductal carcinoma in situ (DCIS) were collected. A total of 320 large-field images were recorded from 58 IC of no special type, 44 invasive lobular carcinomas, 1 invasive mucinous carcinoma, 47 DCIS, 2 lobular carcinomas in situ, and 8 specimens without cancer. Representative images of the main components of the normal breast and the main types of ICs and DCIS were annotated to establish an UFCM atlas. UFCM enables the imaging of the fresh breast tissue sections. Main morphological criteria defined in traditional histopathology such as tissue architecture and cell features can be applied to describe UFCM images content. The generated atlas of the main normal or tumoral tissue features will support the adoption of this optical technology for the intraoperative examination of breast specimens in clinical practice as it can be used to train physicians on UFCM images and develop artificial intelligence algorithms. Further studies are needed to document rare breast lesions.

Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

Mucin-producing tumors of the ovary——preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors

ObjectiveTo investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs).MethodsThis retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance.Results35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%.ConclusionsPatients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Histopathological and Immunohistochemical Evaluation of Malignant Ovarian Tumours

Objective: To determine the frequency and histological types of malignant ovarian tumours using morphological features and immunohistochemistry. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Army Medical College, Rawalpindi Pakistan, Jan 2016 to Dec 2018. Methodology: Newly diagnosed cases of malignant ovarian tumour who had not received chemotherapy were included. Cases of benign ovarian tumours and those who were treated with pre-surgical chemotherapy were excluded. Results: In total, 118 cases of malignant ovarian tumours were evaluated. High-grade serous carcinomas were 61(51.7%), which outnumber others, followed by granulosa cell tumours 17(14.4%), germ cell tumours 13(11%), endometrioid carcinoma 9(7.6%), clear cell carcinoma 4(3.4%), mucinous carcinoma 4(3.4%), low-grade serous carcinoma 2(1.7%) and carcinosarcoma in one case (0.8%). Cancer in the ovary was metastatic in 7(5.9%) cases. No Sertoli Leydig cell tumour, malignant Brenner tumour, embryonal carcinoma or immature teratomas were diagnosed. Conclusion: Surface epithelial tumours were the most common malignancy, followed by granulosa cell tumours and dysgerminoma. An increase in the frequency of ovarian tumours in younger age groups was also noted. Immunohistochemistry was a useful adjuvant diagnostic tool in cases of ovarian malignancy. Metastases to the ovary were mostly gastrointestinal in origin.

Dielectric Characterization of Ex-Vivo Breast Tissues: Differentiation of Tumor Types through Permittivity Measurements.

Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to characterize benign or malignant tumors. Dielectric microwave spectroscopy makes use of an open-ended coaxial probe in the 1-8 GHz frequency range to quickly identify the type of tumor (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma). The experiment was undertaken with data from 70 patients who had already undergone chemotherapy treatment, which helped to electrically map the histological tissues with their electric permittivity. Thus, the variations in the permittivity of different types of tumors reveal distinctive patterns: benign tumors have permittivity values lower than 35, while malignant ones range between 40 and 60. For example, at a frequency of 2 GHz, the measured permittivity was 45.6 for ductal carcinoma, 33.1 for lobular carcinoma, 59.5 for mucinous carcinoma, and 27.6 for benign tumors. This differentiation remains consistent in a frequency range of 1 to 4.5 GHz. These results highlight the effectiveness of these measurements in the classification of breast tumors, providing a valuable tool for quick and accurate diagnosis and effective treatment.

Gastric-type adenocarcinoma of the uterine cervix: clinical features and future directions.

The concept of gastric-type mucinous carcinoma of the uterine cervix (GAS) has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papilloma virus infection. The World Health Organization (WHO) 2020 classification divides cervical tumours into two categories: human papilloma virus-associated and human papilloma virus-independent. Hence, GAS is now classified as an human papilloma virus-independent gastric type. Because clinical studies have reported that GAS is refractory to conventional treatments such as chemotherapy and radiotherapy, especially at an advanced stage, and has aggressive features with widespread dissemination to unusual sites, such as the omentum, peritoneum and distant organs, it is urgent to establish new treatment strategies by comparing the molecular profiles of human papilloma virus-associated adenocarcinomas. A series of genetic mutations characteristic to GAS encourage the development of future treatment strategies such as targeted therapy and immunotherapy.