Mucinous Neoplasm Research Articles

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours

BackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

The value of ultrasonography combined with carbohydrate antigen 125 and 19-9 detection in the diagnosis of borderline ovarian tumors and prediction of recurrence.

This study aimed to investigate the clinical value of ultrasonography combined with tumor markers in the diagnosis and prediction of recurrence of borderline ovarian tumors (BOTs) and analyze the value of the combination of two different auxiliary examinations in the diagnosis and prediction of recurrence of BOTs. Here, 221 patients with BOTs confirmed by postoperative pathology were enrolled. Their clinical data, including the ultrasonography features, tumor markers, and clinicopathological data, were retrospectively analyzed. The statistical data of the 221 cases with BOTs were as follows: 94 (42.5%) with left-sided lesions, 102 (46.2%) with right-sided lesions, and 25 (11.3%) with bilateral lesions. Moreover, 93 cases (42.1%) had a borderline serous tumor, 110 (49.8%) had a borderline mucinous tumor, 12 (5.4%) had a borderline serous mucinous tumor, 2 (0.9%) had a borderline endometrioid tumor, 1 (0.5%) had a borderline Brenner tumor, and 2 (0.9%) had a clear cell BOT. There were 104 cases (47.1%) with a tumor diameter of ≤10 cm and 117 cases (52.9%) with a tumor diameter of >10 cm as suggested by ultrasonography. There were 89 cases (40.3%) with septation, 44 (19.9%) with papilla, and 97 (43.9%) with blood flow as demonstrated by ultrasonography. Carbohydrate antigen 125 (CA 125) was elevated in 132 cases (59.7%), and CA 19-9 was elevated in 52 cases (23.5%). In general, BOTs are difficult to diagnose preoperatively and have a certain recurrence rate. Ultrasonography combined with CA 125 and CA 19-9 is significant for the preoperative diagnosis and selection of surgical modality for BOTs and could be used as a guideline to achieve good preoperative preparation and avoid secondary surgery.

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran.

Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progression of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in the development of EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes. A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing. While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group. The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

Postmenopausal woman with 24 kgs ovarian mucinous cystadenoma: a rare case report

A case of a 53-year-old postmenopausal woman presenting a giant ovarian cystic mucinous tumor weighing 24 kg is reported here. When she was seen first at our outpatient clinic, she had gross abdominal distension since 2 years, and she complained of unbearable aggressive pain. Her computed tomography (CT) scan was done which came suggestive of ovarian serous cystadenoma of large massive size 35 x 40 x 32 cm with moderate ascites. On exploratory laparotomy, a giant, totally cystic, vascularized and smooth mass attached to the right ovary was encountered. On the postoperative tenth day, she was discharged without any problem. Histopathology report of the right ovarian cystic mass came suggestive of multiloculated cyst with capsule intact with Borderline Mucinous tumor of right ovary weighing 24 kg. This is both one of the largest known examples in the literature and the largest ovarian cyst ever seen at our institution.

ABERRANT EXPRESSION OF COL14A1, CELRS3, and CTHRC1 IN BREAST CANCER СELLS.

Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling. To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC. The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients. Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs andmembers of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes. The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.

Role of magnetic resonance imaging in the differentiation of mucinous ovarian carcinoma and mucinous borderline ovarian tumors.

This study was carried out to investigate the differentiation of mucinous borderline ovarian tumor from mucinous ovarian carcinoma using magnetic resonance imaging. We evaluated 77 women patients who underwent abdominal magnetic resonance imaging due to pelvic mass. magnetic resonance imaging was reviewed by an experienced radiologist. A total of 70 women patients were included in the study. The magnetic resonance imaging features were retrospectively evaluated and compared between the two pathologies. There was no difference between the two groups in terms of maximum tumor size. Age at diagnosis was 56.29±11.92 in the mucinous ovarian carcinoma group and 44.74±13.60 in the mucinous borderline ovarian tumor group (p<0.05). A significant difference was found between the two groups, and it was observed that mucinous borderline ovarian tumors appeared in the younger age group compared to mucinous ovarian carcinomas. Presence of ascites, peritoneal dissemination, lymphadenopathy, and mural nodules was found significantly more frequently in mucinous ovarian carcinomas than in mucinous borderline ovarian tumors. Honeycomb appearance was found more frequently in mucinous borderline ovarian tumor patients than in mucinous ovarian carcinoma patients. magnetic resonance imaging findings of these two pathologies overlapped considerably. Compared with mucinous borderline ovarian tumors, mucinous ovarian carcinomas frequently had mural nodules larger than 5 mm, larger tumor size, peritoneal dissemination, and abnormal ascites.

Disparity in the era of personalized medicine for epithelial ovarian cancer.

The treatment of high-grade serous ovarian cancer and high-grade endometrioid ovarian cancer has seen significant improvements in recent years, with BRCA1/2 and homologous recombination status guiding a personalized approach which has resulted in improved patient outcomes. However, for other epithelial ovarian cancer subtypes, first-line treatment remains unchanged from the platinum-paclitaxel trials of the early 2000s. In this review, we explore novel therapeutic approaches being adopted in the treatment of clear cell, mucinous, carcinosarcoma and low-grade serous ovarian cancer and the biological rational behind them. We discuss why such disparities exist, the challenges faced in conducting dedicated trials in these rarer histologies and look towards new approaches being adopted to overcome them.

A Case Study on Jelly Belly

Pseudomyxoma peritonei (PMP) is a rare malignant growth characterised by the progressive accumulation of mucus-secreting (mucinous) tumour cells within the abdomen and pelvis. The common manifestations in patients are abdominal distension and appendicitis-like symptoms. Computed tomography scan with contrast of the chest, abdomen and pelvis is currently the imaging modality of choice for the diagnosis of PMP. As per the current guideline, the curative treatment for PMP is complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy. The purpose of this article is to highlight the rarity of the disease and the typical presenting symptoms, the trends in diagnosis and treatment, the role of nurses and the challenges faced in taking care of patients with rare malignancies receiving treatment.

Can Preoperative Complete Blood Count Parameters and Tumor Markers Predict The Differential Diagnosis of Mucinous Ovarian Tumors?

Can Preoperative Complete Blood Count Parameters and Tumor Markers Predict The Differential Diagnosis of Mucinous Ovarian Tumors?

Clinicopathological analysis of ovarian mucinous tumor

Clinicopathological analysis of ovarian mucinous tumor

Mucinous neoplasms of the appendix - A clinicopathologic study of 21 cases with special insight into current classification &amp; controversies.

Background : Appendiceal mucinous neoplasms are rare and heterogenous disease which often clinically present as appendicitis. There are many controversies regarding the classification of mucinous neoplasms of the appendix.&#x0D; Aims and Objectives: Our aim of this study was to study different types of mucinous neoplasms of appendix based on current ( WHO 2019) classification, their clinical and radiological presentations and controversies regarding their diagnosis.&#x0D; Materials and Methods: This was a retrospective study done in a tertiary care hospital. We studied clinical presentations of 21 cases along with the histopathological study of respective appendectomy specimens .&#x0D; Results: Out of 21 cases, 3 (14.28%) cases were serrated polyp, 9 cases (42.85%) were Low grade appendiceal mucinous neoplasm (LAMN), 3 cases (14.28%) were high grade appendiceal neoplasm (HAMN) and 6 (28.57%) cases were mucinous adenocarcinoma. In this study we have discussed in brief about regarding the current classification and controversies of appendiceal mucinous neoplasms.&#x0D; Conclusion: Mucinous neoplasms of the appendix are complex lesions with many controversies. Oversimplification in the recent classification may add to more complexity. Reintroduction of the old terminology of Mucinous Tumour of Uncertain Malignant Potential might save histopathologists from potential litigation.

A Case of Huge Mucinous Cystadenoma

Introduction: Ovarian mucinous cystadenoma is a benign tumour that arises from the surface epithelium of ovary. Aim/Objectives: To report the occurrence of a huge benign ovarian tumour. Case Report: A 24-year-old female presented to the OPD with complaints of pain lower abdomen, loss of appetite, and abdominal distension since 4 months. Her USG and CT scan reports showed it to be case of mucinous cystadenoma. She underwent laparotomy with left-sided cystectomy. Her Histopathological report showed borderline mucinous tumour. Peritoneal washing showed negative for atypical cells. Discussion: Giant tumours are now a rare presentation due to their early diagnosis due to routine check-ups on ultrasound

Histologic and genomic characterization of a primary mucinous carcinoma of the skin

AimsPrimary skin mucinous carcinoma is a rare sweat gland neoplasm with a high local recurrence rate after conventional excision but a low distant-metastasis rate. The genetic underpinning of skin mucinous carcinoma is presently unknown. Here, we sought to define whether the repertoire of somatic mutations of a primary mucinous carcinoma of the skin would be similar to that of mucinous breast carcinomas, given the histologic similarities between these tumor types. Methods and resultsThe tumor was situated in the dermis and partially involved the subcutaneous fat. Tumor cells were suspended in periodic acid–Schiff diastaseresistant- positive mucin lakes and expressed cytokeratin 7, synaptophysin and estrogen receptor. DNA samples extracted from microdissected tumor and matched normal tissue were subjected to massively parallel sequencing targeting 410 cancer-related genes. The skin mucinous tumor was found to have a low tumor mutation burden, but to harbor a clonal GATA3 frameshift mutation (p.T418Hfs*89) and amplification of FOXA1, genes not uncommonly altered in breast mucinous carcinomas. ConclusionsIn this primary skin mucinous carcinoma, GATA3 and FOXA1 driver genetic events were identified, consistent with a possible developmental relationship between skin and breast mucinous neoplasms.

The Importance of Il8 Gene Expression and Il-8 A251t in Diagnosis and Prognosis of Ovarian Cancer in Iraqi Women

The present study aimed to shed light on the association between the gene expression of IL8 and its genetic polymorphism IL-8 A251T in the incidence and pathogenesis of ovarian cancer. A total of 43 Paraffin-embedded tissue blocks from patients with different stages of newly diagnosed ovarian cancer were provided by certain Iraqi hospitals as well as 14 samples of patients with benign ovarian tumors tissues as a control group were used in this study. In the present study, the level of IL8 gene expression was investigated by comparing it with that of benign tumors, the results detected that IL-8 mRNA was expressed in 47(81.02%) of samples, 36 samples with ovarian cancer and 11 benign ovarian. IL-8 mRNA levels in ovarian cancer tissues were statically significant higher than those in benign ovarian tissue (P=0.0328&lt;0.05). The samples were divided into high and low mRNA-expression depending on the mean value of IL8 gene expression in benign tumors which used as a cutoff, the results showed that samples with high mRNA-expressing 25(69.4%) which showed high significant differences compare with samples that showed low expressing 11(30.55%) (P value=0.0028&lt;0.01). In correlation with histopathological type of ovarian tumors, mucinous tumors showed statistically significant difference in compare with other histopathologic tumor type (P=0.0516,&lt;0.05). According to the tumor stages, statistically significant difference was found between 31(86.11%) of samples with stage I which showed the highest level of expression and 5(13.88%) of samples with stage III (P value=0.0410&lt;0.05). For A251T polymorphism, the result showed that 21(58.33%) patients were heterozygous A/T, 14(38.88%) were homozygous T/T, and 1(2.77%) was homozygous A/A. For patients with benign ovarian tumors 11(91.66%) were heterozygous A/T, 1(8.33%) was homozygous T/T, and no one of the patients were homozygous for the A/A genotype. High significant prevalence of the IL-8 251T allele was detected in both ovarian cancer patients (P value 0.0047 &lt;0.01) and patients with benign ovarian tumors (P value 0.014 &lt;0.02) as compared with IL-8 251A allele. In the present study the association of the A251T polymorphism with ovarian cancer were investigated by attending to levels of IL-8 mRNA in benign and malignant ovarian tissues related with the respective genotypes. In benign ovarian tumors statically analysis showed that there were no significant differences between genotypes, while for cancer samples, the average of IL-8 gene expression in ovarian cancer patients carrying +251TT genotype was highly significant than that in ovarian cancer patients with the +251AT and +251AA genotypes (p value= 0.0037&lt;0.01). In conclusion, the results reflected the possibility of detecting the IL8 gene transcript in benign as well as the malignant ovarian tissues but with wide differences in the sample percentages and level of gene expression which in turn reflect the value of IL8 gene as a useful tool for discriminating malignant breast tumors from non-malignant ones. On the other hand the high level of gene expression associated with stage I of tumor may be reveals the diagnostic value of this gene for early diagnosis of ovarian cancer. The results showed that the genetic variation of IL-8 gene influences susceptibility to ovarian cancer, we also suggested that the TT genotype of IL-8 -251A/T may associate with increase the risk of ovarian cancer in Iraqi women because of altered IL-8 gene expression.

The impact of omentectomy on cause-specific survival of Stage I-IIIA epithelial ovarian cancer: A PSM-IPTW analysis based on the SEER database.

Routine omentectomy is generally performed during surgery for patients with epithelial ovarian cancer (EOC). The current study aims to evaluate the impact of omentectomy on cause-specific survival of Stage I-IIIA EOC patients. Patients who presented with clinical Stage I-IIIA serous, clear cell, endometrioid, and mucinous ovarian cancers were selected from the SEER Database for the period between 2004 and 2018. We extracted clinicopathological data and surgical information with the focus on the performance of omentectomy and lymphadenectomy. Binary logistic regression and recursive partitioning analyses were conducted to identify the significant factors for the performance of omentectomy during surgery. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were utilized to balance confounding factors. Multivariate, exploratory subgroup analyses and sensitivity analyses were conducted to evaluate the impact of omentectomy on cause-specific survival (CSS). A total of 13,302 patients with EOC were enrolled in the study. The cohort comprised 3,569 endometrioid, 4,915 serous, 2,407 clear cell, and 2,411 mucinous subtypes. A total of 48.62% (6,467/13,302) of patients underwent the procedure of omentectomy during primary surgery, and only 3% absolute improvement in CSS at the individual level was observed, without statistical significance based on multivariate analysis. According to the regression-tree model with recursive partitioning analysis, the procedure of lymphadenectomy was found to be the strongest factor to distinguish the performance of omentectomy, followed by the tumor stage. Patients who underwent omentectomy were more likely to be managed in Stage I than those who underwent lymphadenectomy. After PSM-IPTW adjustment, the inclusion of omentectomy in the initial surgical procedure did not demonstrate a beneficial impact on CSS compared with those who did not undergo the procedure. Exploratory subgroup analysis indicated that the performance of omentectomy improved 5-year CSS in Stage II-IIIA patients. In the sensitive analyses for various tumor stages, omentectomy appeared to benefit only Stage II patients. However, patients across various stages seemed to benefit from the performance of lymphadenectomy, irrespective of the performance of omentectomy on them. Routine omentectomy may not be associated with survival benefit for patients with a grossly normal-appearing omentum, especially for those with clinical Stage I epithelial ovarian cancers.

Immunohistochemical phenotype of fallopian tubes in patients with different grades of serous ovarian carcinoma

During recent years, there is an accumulating evidence that high grade ovarian carcinoma is developed from the fallopian tube epithelial lesions. However, is not yet completely understood and still represents the subject of investigation. We investigated the immunohistochemical phenotype of matched fallopian tubes from the patients with different types and malignancy grades of ovarian carcinoma. Matched fallopian tubes from ovarian cancer patients were available in 260 cases, including mucinous borderline tumor (n=25), mucinous carcinoma (n=15), serous borderline tumor (n=90), low grade serous carcinoma (n=72) and high grade serous carcinoma (n=48). Immunohistochemical investigation included markers of proliferation (Ki67), apoptosis (Bcl2, p53), hormone receptors (ER, PR), epithelial differentiation (CK7), mesenchymal differentiation (vimentin, calretinin) and stem cells (CD44). The results indicate that the presence of fallopian tube carcinoma in situ is significantly correlated with the presence of high grade ovarian serous carcinoma (r=0.44, p&amp;#60;0.001), whilst there was no significant association with low grade and borderline serous tumors or mucinous tumors.

Distribution of tumor-associated macrophages and M1/M2 polarization in different types and grades of ovarian tumors

Ovarian cancer represents one of the major causes of gynaecologic cancer mortality worldwide. Tumor-associated macrophages (TAM) are associated with the development and progression of ovarian cancer. TAMs are mainly represented by two types M1 and M2. We investigated the distribution of total, M1, M2 macrophages, tumor cell/macrophage ratio and M1/M2 ratio in mucinous and serous ovarian tumors. The study results showed that total TAM count is significantly higher in serous ovarian tumors, compared to mucinous tumors and the highest infiltration rate is detected in high-grade serous ovarian carcinomas. In addition, the number of M2 macrophages is significantly increased in higher-grade serous ovarian carcinomas. The evaluation of tumor/cell macrophage ratio could be used as an objective measure of macrophage infiltration in ovarian tumors.

Culture and Imaging of Ex Vivo Organotypic Pseudomyxoma Peritonei Tumor Slices from Resected Human Tumor Specimens.

Pseudomyxoma peritonei (PMP) is a rare condition that results from the dissemination of a mucinous primary tumor and the resultant accumulation of mucin-secreting tumor cells in the peritoneal cavity. PMP can arise from various types of cancers, including appendiceal, ovarian, and colorectal, though appendiceal neoplasms are by far the most common etiology. PMP is challenging to study due to its (1) rarity, (2) limited murine models, and (3) mucinous, acellular histology. The method presented here allows real-time visualization and interrogation of these tumor types using patient-derived ex vivo organotypic slices in a preparation where the tumor microenvironment (TME) remains intact. In this protocol, we first describe the preparation of tumor slices using a vibratome and subsequent long-term culture. Second, we describe confocal imaging of tumor slices and how to monitor functional readouts of viability, calcium imaging, and local proliferation. In short, slices are loaded with imaging dyes and are placed in an imaging chamber that can be mounted onto a confocal microscope. Time-lapse videos and confocal images are used to assess the initial viability and cellular functionality. This procedure also explores translational cellular movement, and paracrine signaling interactions in the TME. Lastly, we describe a dissociation protocol for tumor slices to be used for flow cytometry analysis. Quantitative flow cytometry analysis can be used for bench-to-bedside therapeutic testing to determine changes occurring within the immune landscape and epithelial cell content.

Abstract B027: Circulating tumor DNA in colorectal carcinomatosis: Detection and prognostic value

Abstract Background: Circulating tumor DNA (ctDNA) of patients with colorectal peritoneal metastases (PM) was obtained to identify prognostic factors associated for ctDNA detection and with overall survival (OS). Prior studies have identified a correlation between ctDNA detection and OS in colorectal liver metastases (CRLM) and after resection of primary tumors. However, detection rates for PM may be lower than other metastatic sites. Methods: Peripheral blood was drawn from 152 patients after diagnosis with PM with or without other synchronous sites of disease. Patients who underwent cytoreduction were excluded. Next-generation sequencing of a panel of 70 genes commonly mutated in colorectal cancer was performed on all samples. Mutations were identified and variant allele frequencies (VAFs) calculated. Clinical data including OS from time of CRCC diagnosis, tumor grade, tumor histology, synchronous non-peritoneal metastases and patient demographics were obtained from medical records .Chi-squared tests were performed to compare differences in ctDNA detection based on clinical factors, and Cox regression analyses were performed to identify associations with ctDNA characteristics and OS. Results: The overall detection rate of any mutation in ctDNA was 74.3% (110/145 patients). The most frequently detected mutations were TP53 (55%), APC (47%), KRAS (32%), and PIK3CA (14%). Sensitivity for detecting individual mutations ranged from 50%-63%. Mucinous and signet-ring cell histology were more common in patients with PM alone (Mucinous: 37% vs 24%, p=0.0003, Signet Ring Cell: 10% vs. 2.2%, p=0.0001) and associated with lower sensitivity (mucinous: 59%, signet-ring cell: 57% and adenocarcinoma 85%, p=0.002). Synchronous CRLM were associated with increased detection compared to PM alone (88% vs. 68%, p=0.011). After adjustment for differences in histology, synchronous CRLM (OR 3.32, 95CI: 1.52-8.02, p=0.016) was associated with higher detection rates. Grade was not associated with detection (moderately differentiated: 79%, poorly differentiated: 74%, p=0.81). Detection of any ctDNA was associated with a trend towards worse OS (HR 2.18, 95% CI: 0.98-4.95, p=0.06). KRAS (HR 2.02, 95% CI: 1.14-3.60, p=0.017) and PIK3CA (HR 2.26, 95% CI: 1.07-4.78, p=0.033) ctDNA detection was associated worse OS. Detection of multiple mutations (HR: 0.85, 95% CI 0.50-1.42, p=0.52) and maximum VAF (HR 0.99, 95% CI: 0.97- 1.01, p=0.17) were not associated with OS. Conclusion: ctDNA detection is lower in patients with PM alone compared to those with PM and CRLM. Mucinous tumors had lower rates of ctDNA detection after accounting for extra-PM metastases. Presence of ctDNA is associated with a trend towards worse OS, especially for patients with detectable mutations in KRAS or PIK3CA. Quantification of ctDNA by number of mutations or VAF was not associated with OS. Interpretation of ctDNA results for PM patients should take into consideration the lower sensitivity in the absence of other metastatic sites, but may have prognostic utility. Citation Format: Abhineet Uppal, Michael G. White, George J. Chang, Scott Kopetz, John Paul Y. C. Shen. Circulating tumor DNA in colorectal carcinomatosis: Detection and prognostic value [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B027.