[Primary mucinous gland lesions of fallopian tube: a clinicopathological analysis of fourteen cases].

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.

The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors.

BACKGROUND: Primary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. METHODS: Seventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. RESULTS: Mutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). CONCLUSION: p53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Significance of MUC1 and ß-Catenin Localization in Mucinous Carcinoma of the Breast.

BACKGROUND/AIM: There are two main subtypes of mucinous carcinoma (MC) based on the quantification of the mucinous component: the pure variant (pMC) and the mixed variant (mMC). pMC has been subdivided into pure A with a hypocellular variant, and pure B with a hypercellular variant. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological features of 99 patients with MC who were treated at our institution from January 2002 to December 2014. We evaluated the expression profiles of markers, including mucin (MUC) family members, in the patients groups representing different MC subtypes by performing immunohistochemistry to identify factors involved in the differentiation and progression of MCs. RESULTS: Among the 99 patients, 76 (76.8%) had pure mucinous carcinomas (pMC) and the other 23 (23.2%) had mixed mucinous carcinomas (mMC). Of the pMCs, 54 were pure A and 22 were pure B. The prognosis was worse for pure B than pure A and worse for mMC than pMC. Although there was no significant difference in clinicopathological factors between the pure A and pure B groups, immunohistochemical staining revealed differences in the localization of mucin MUC1 and ß-catenin. A comparison of the pMC and mMC cases revealed more lymphovascular invasion in mMC and differences in the localization of ß-catenin between the two groups. CONCLUSION: The patients' prognoses were significantly poorer depending on the histologic subtype (in the order pure A, pure B, and mixed). MUC1 localization and ß-catenin were revealed as independent predictors contributing to the poorer prognosis.

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.

INTRODUCTION: Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line. PATIENTS AND METHODS: PTOs were fabricated from tumor specimens obtained from patients with AC undergoing cytoreductive surgery with HIPEC. PTOs underwent HIPEC treatment with bromelain, cisplatin, and mitomycin C (MMC) at 37 °C and 42 °C with and without bromelain pretreatment. RESULTS: From October 2020 to May 2023, 16 specimens were collected from 13 patients with low-grade (12/16, 75%) and high-grade AC (4/16, 25%). The mucin-depleting effects of bromelain were most significant in combination with N-acetylcysteine (NAC) compared with bromelain (47% versus 10%, p = 0.0009) or NAC alone (47% versus 12.8%, p = 0.0027). Bromelain demonstrated > 31% organoid viability reduction at 60 min (p < 0.001) and > 66% in 48 h (p < 0.0001). Pretreatment with bromelain increased cytotoxicity of both cisplatin and MMC HIPEC conditions by 31.6% (p = 0.0001) and 35.5% (p = 0.0001), respectively. Ki67, CK20, and MUC2 expression decreased after bromelain treatment; while increased caspase 3/7 activity and decreased Bcl-2 (p = 0.009) and Bcl-xL (p = 0.01) suggest induction of apoptosis pathways. Furthermore, autophagy proteins LC3A/B I (p < 0.03) and II (p < 0.031) were increased; while ATG7 (p < 0.01), ATG 12 (p < 0.04), and Becline 1(p < 0.03), expression decreased in bromelain-treated PTOs. CONCLUSIONS: Bromelain demonstrates cytotoxicity and mucolytic activity against appendiceal cancer organoids. As a pretreatment agent, it potentiates the cytotoxicity of multiple HIPEC regimens, potentially mediated through programmed cell death and autophagy.

Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma.

BACKGROUND: Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in-depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies. METHODS: We integrated single-cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three-dimensional bioprinting technique, canonical ex vivo co-culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME. RESULTS: This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte-mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2-phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand-receptor-based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications. CONCLUSIONS: Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA. KEY POINTS: Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA.

Axillary lymph node metastasis in pure mucinous carcinoma of breast: clinicopathologic and ultrasonographic features.

BACKGROUND: The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC). METHODS: A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM. RESULTS: The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338). CONCLUSIONS: Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.

Establishment and characterization of novel high mucus-producing lung tumoroids derived from a patient with pulmonary solid adenocarcinoma.

Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production. The tumoroids were derived from the malignant pleural effusion of a patient with lung cancer and have been successfully developed for long-term culture (> 11 months). Karyotyping by fluorescence in situ hybridization using an alpha-satellite probe showed that tumoroids harbored aneuploid karyotypes. Subcutaneous inoculation of PDT-LUAD#99 lung tumoroids into immunodeficient mice resulted in tumor formation, suggesting that the tumoroids were derived from cancer. Xenografts from PDT-LUAD#99 lung tumoroids reproduced the solid adenocarcinoma with mucin production that was observed in the patient's metastatic lymph nodes. Immunoblot analysis showed MUC5AC secretion into the culture supernatant of PDT-LUAD#99 lung tumoroids, which in contradistinction was barely detected in the culture supernatants of NCI-A549 and NCI-H2122 pulmonary adenocarcinoma cells known for their mucin-producing abilities. Here, we established a novel high-mucus-producing lung tumoroids from a solid adenocarcinoma. This preclinical model may be useful for elucidating the pathogenesis of mucus-producing lung cancer.

Meta-analysis of SATB2 immunohistochemical expression in colorectal cancer versus primary ovarian mucinous neoplasms.

BACKGROUND: Reliably distinguishing primary ovarian mucinous neoplasms (POMNs) from metastatic colorectal cancers (CRCs) is both challenging to the histopathologist and of great clinical importance. Special AT-rich sequence binding protein-2 (SATB2) has emerged as a useful diagnostic immunohistochemical marker of colorectal cancer. This meta-analysis compares SATB2 expression in POMNs and CRC. METHODS: A systematic literature search for relevant studies was conducted. Meta-analysis of SATB2 positivity was undertaken using a random effects model. RESULTS: Seven studies including 711 CRCs and 528 POMNs were included. SATB2 positivity was seen in 81 % (95 % CI: 72-88 %) of CRCs and 4 % (95 % CI: 1-11 %) of POMNs. Variation was seen in immunohistochemical methods used for SATB2 detection and threshold for positivity. CONCLUSION: SATB2 staining remains high in CRC and low in POMNs, supporting its use in differentiating these two pathologies with vastly differing prognosis and treatment.

POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.

Colorectal mucinous adenocarcinoma (MAC) is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC). This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs) between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

Metabolic Syndrome Accelerates the Age-Related Increase of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

OBJECTIVES: Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. METHODS: A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. RESULTS: Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28-3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14-6.72; P = 0.003). CONCLUSIONS: The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.

Infiltrative pattern of invasion is independently associated with shorter survival and desmoplastic stroma markers FAP and THBS2 in mucinous ovarian carcinoma.

AIMS: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer histotype with generally good prognosis when diagnosed at an early stage. However, MOC with the infiltrative pattern of invasion has a worse prognosis, although to date studies have not been large enough to control for covariables. Data on reproducibility of classifying the invasion pattern are limited, as are molecular correlates for infiltrative invasion. We hypothesized that the invasion pattern would be associated with an aberrant tumour microenvironment. METHODS AND RESULTS: Four subspecialty pathologists assessed interobserver reproducibility of the pattern of invasion in 134 MOC. Immunohistochemistry on fibroblast activation protein (FAP) and THBS2 was performed on 98 cases. Association with survival was tested using Cox regression. The average interobserver agreement for the infiltrative pattern was moderate (kappa 0.60, agreement 86.3%). After reproducibility review, 24/134 MOC (18%) were determined to have the infiltrative pattern and this was associated with a higher risk of death, independent of FIGO stage, grade, and patient age in a time-dependent manner (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 3.0-34.5). High stromal expression of FAP and THBS2 was more common in infiltrative MOC (FAP: 60%, THBS2: 58%, both P < 0.001) and associated with survival (multivariate HR for FAP: 1.5 [95% CI 1.1-2.1] and THBS2: 1.91 [95% CI 1.1-3.2]). CONCLUSIONS: The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

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

BACKGROUND: The 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). METHODS: Immunohistochemistry 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. RESULTS: Among 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. CONCLUSION: Claudin18.2 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 role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma.

Human epidermal growth factor receptor 2 (HER2) is a prognostic biomarker and therapeutic target in carcinomas of the breast, stomach and colon. In 2018, clinical trial data confirmed the prognostic and predictive role of HER2 in uterine serous carcinoma, with a demonstrated survival benefit from combined chemotherapy and anti-HER2 targeted therapy in patients with advanced or recurrent disease. Approximately one-third of uterine serous carcinomas demonstrate HER2 protein overexpression and/or gene amplification and HER2 immunohistochemistry, supplemented by in situ hybridisation in equivocal cases, is fast becoming a reflex ancillary test at time of diagnosis. The potential role of HER2 in gynaecological tumours other than uterine serous carcinoma is yet to be firmly established. With the advent of personalised medicine, routine tumour sequencing and pursuit of targeted therapies, this is a field currently under active investigation. Emerging data suggest triaging endometrial carcinomas for HER2 analysis based on molecular classification may be superior to histotype-based testing, with copy-number high/p53 mutant tumours enriched for HER2 overexpression or amplification. Accordingly, many carcinosarcomas and a subset of clear cell and high-grade endometrioid carcinomas may be eligible for HER2 targeted therapy, although any clinical benefit in this context is currently undefined. For ovarian carcinomas, combined data support the role of HER2 as a prognostic biomarker, however its use as a therapeutic target is yet to be elucidated through clinical trials. In the cervix, reported rates of HER2 overexpression vary and are generally low, and currently there is insufficient evidence to justify routine HER2 testing in this context. Limited data suggest HER2 holds promise as a prognostic and predictive biomarker in vulvar Paget disease. Future clinical trials, with pathologist input to develop and refine site-specific scoring criteria, are required to establish what role HER2 might play more broadly in gynaecological cancer care.

Evaluation of MUC1, MUC2, MUC5AC, and MUC6 Expression Differences in Lung Adenocarcinoma Subtypes by Using a Final Immunoreactivity Score (FIRS).

OBJECTIVE: Lung adenocarcinomas are divided into acinar, lepidic, papillary, micropapillary, and solid predominant subtypes according to the current World Health Organization (WHO) classification. We designed this retrospective study to demonstrate profiles of MUC expression (MUC1, MUC2, MUC5AC, and MUC6) of different histologic patterns within the same tumor among pulmonary adenocarcinomas and investigate correlations of MUC expression with clinicopathologic features. MATERIAL AND METHOD: We analyzed the expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) in a series of 99 resected lung adenocarcinomas, which included a total of 193 patterns (71 acinar, 30 lepidic, 25 papillary, 20 micropapillary, 34 solid and 13 mucinous) and calculated a final immune reactivity score (FIRS) per tumor. RESULTS: MUC1 IRS scores were significantly higher in lepidic and solid patterns compared with mucinous patterns (p=0.013). MUC2 expression was seen only in three cases (1 acinar, 2 mucinous). MUC5AC and MUC2 expression was more common in mucinous patterns (p < 0.001 and p=0.028, respectively). MUC6 expression was only detected in seven patterns and the expression was weak. No significant difference was seen among histologic patterns for the staining scores of MUC6. Mucinous adenocarcinoma differed from other histologic subtypes regarding MUC1 and MUC5AC expression. Mucinous adenocarcinoma showed less MUC1 expression with lower IRS scores and higher MUC5AC expression. Tumor size (p=0.006), lymphatic invasion (p=0.018), vascular invasion (p=0.025), perineural invasion (p=0.019), MUC1 IRS scores (p=0.018), and MUC1 IRS scores > 8.5 (p=0.018) were significant predictors for lymph node metastasis. CONCLUSION: An alternative scoring for MUC1 can be used as a predictor for lymph node metastasis regardless of the histologic subtype.

Clinicopathological features of pulmonary mucinous adenocarcinoma: A descriptive analysis.

BACKGROUND: Mucinous adenocarcinoma is a rare subtype of lung cancer characterized by abnormal mucin production. We sought to investigate the clinical and pathological features of pulmonary mucinous adenocarcinomas and to identify prognostic factors. METHODS: This was a single-institution retrospective review of patients with pulmonary mucinous adenocarcinoma diagnosed between January 1, 2015 and December 31, 2020. Descriptive analysis included demographics, diagnostic data, and treatment modalities. The primary outcome was overall survival (OS). RESULTS: Fifty-six patients were included in the study. Median age was 65 years (range: 26-84), 30 (54%) were female, 48 (86%) had a smoking history, and 41 (73%) patients had ECOG performance status 0-1. Nearly half (26, 46%) were stage IV at presentation, while 11 (20%) presented as stage I, 10 (18%) stage II, and 9 (16%) stage III. Biomarker testing increased through the study period. Where performed, 4/48 (8%) cases were ALK positive, but there were no EGFR cases identified (0/36). Only 3/20 cases had PD-L1 expression >50%. Curative intent therapy was performed in 23 patients (17 had surgery +/- chemotherapy/radiation, 4 had radiotherapy alone, 2 had chemoradiation). Median OS in the entire population was 16.1 months (m). OS by stage was 50.0m for stage I, not reached for stage II, 20.7m for stage III, and 8.1m for stage IV. CONCLUSIONS: The overall prognosis of pulmonary mucinous adenocarcinoma appears similar to that of non-mucinous adenocarcinomas, with distinct differences noted in the incidence of oncogenic driver mutations, particularly an absence of EGFR mutations.

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach.

The morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad, and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the World Health Organisation (WHO) Classification of female genital tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intra-operative handling of these tumours. A number of diagnostic issues remain unresolved, highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia.

Expression of CD10 and CD15 in colorectal mucinous and signet ring adenocarcinomas and its relation to clinicopathological features and prognosis.

BACKGROUND: CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known. OBJECTIVE: We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression. METHODS: Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done. RESULTS: Compared to adenomas, CD15 expression was significantly higher in MSA (p= 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p= 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients. CONCLUSIONS: CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression.

Novel Criteria for Intratumoral Budding with Prognostic Relevance for Colon Cancer and Its Histological Subtypes.

Peritumoral budding and intratumoral budding (ITB) are important prognostic factors for colorectal cancer patients. Scientists worldwide have investigated the role of budding in tumor progression and its prognosis, but guidelines for reliably identifying tumor buds based on morphology are lacking. In this study, next-generation tissue microarray (ngTMA®) construction was used for tumor bud evaluation, and highly detailed rule-out annotation was used for tumor definition in pancytokeratin-stained tissue sections. Initially, tissues of 245 colon cancer patients were evaluated with high interobserver reliability, and a concordance of 96% was achieved. It was shown that high ITB scores were associated with poor distant metastasis-free survival (p = 0.006 with a cut-off of ≥10 buds). This cut-off was defined as the best maximum value from one of two/three ngTMA® cores (0.6 mm diameter). ITB in 30 cases of mucinous, medullary, and signet ring cell carcinoma was analyzed for the subsequent determination of differences in tumor bud analyses between those subtypes. In conclusion, blinded randomized punched cores in the tumor center can be useful for ITB detection. It can be assumed that this method is suitable for its adoption in clinical routines.