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BioRxiv : the Preprint Server For... Jun 2023Esophageal adenocarcinoma arises from Barrett's esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation....
Esophageal adenocarcinoma arises from Barrett's esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue-mechanics and spatial proteomics of 64 samples from 12 patients' paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, revealed shared and patient-specific progression characteristics. The classic metaplastic replacement of epithelial cells was paralleled by metaplastic changes in stromal cells, ECM and tissue stiffness. Strikingly, this change in tissue state at metaplasia was already accompanied by appearance of fibroblasts with characteristics of carcinoma-associated fibroblasts and of an NK cell-associated immunosuppressive microenvironment. Thus, Barrett's esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporating stromal reprogramming.
PubMed: 37333362
DOI: 10.1101/2023.06.08.544265 -
Cancers Nov 2023Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional... (Review)
Review
Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include rearrangements in 50% to 56% of mucoepidermoid carcinomas (), 77% to 100% of metaplastic thymomas (), and 6% of B2 and B3 thymomas (); rearrangements in NUT carcinomas (most commonly ); rearrangement in hyalinizing clear cell carcinoma (); and rearrangement in a thymoma (). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.
PubMed: 38067300
DOI: 10.3390/cancers15235596 -
Cancers Mar 2023Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of...
BACKGROUND
Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified.
METHODS
We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis.
RESULTS
The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, = 0.1340) after PSM.
CONCLUSION
Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.
PubMed: 36900347
DOI: 10.3390/cancers15051556 -
Iranian Journal of Pathology 2022Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal...
BACKGROUND & OBJECTIVE
Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma.
METHODS
The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute.
RESULTS
A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively.
CONCLUSION
Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to diagnosis of the process.
PubMed: 36247506
DOI: 10.30699/IJP.2022.541798.2757 -
Archives of Pathology & Laboratory... Feb 2018Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and its higher-grade counterpart, dedifferentiated liposarcoma (DDL), are extraordinarily rare tumors... (Review)
Review
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and its higher-grade counterpart, dedifferentiated liposarcoma (DDL), are extraordinarily rare tumors in the breast. The main differential diagnostic consideration of primary breast ALT/WDL is malignant phyllodes tumor with liposarcomatous differentiation, and the main differential diagnostic consideration of DDL in the breast is metaplastic breast carcinoma, particularly the spindle cell type, with heterologous sarcomatous differentiation. These differential diagnoses may be particularly challenging when evaluating limited core needle biopsy sampling. MDM2 and/or CDK4 protein overexpression and gene amplification are beneficial ancillary studies that can help establish the diagnosis of primary breast ALT/WDL and DDL, and effectively rule out the diagnoses of malignant phyllodes tumor and metaplastic breast carcinoma.
Topics: Breast Neoplasms; Female; Humans; Lipoma; Liposarcoma
PubMed: 29372852
DOI: 10.5858/arpa.2016-0380-RSR2 -
International Journal of Molecular... Jul 2023Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates... (Review)
Review
Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.
Topics: Humans; Barrett Esophagus; Esophageal Neoplasms; Adenocarcinoma; Risk Factors; Metaplasia
PubMed: 37511077
DOI: 10.3390/ijms241411318 -
Archives of Pathology & Laboratory... Apr 2022Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers.
CONTEXT.—
Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers.
OBJECTIVE.—
To determine association of histologic type (HT) and RS, specifically high-risk RS.
DESIGN.—
We used RSs linked to Surveillance, Epidemiology, and End Results Program registries of invasive breast cancers diagnosed in 2004 through 2015. Multivariable logistic regression was used to evaluate association between HT and high-risk RS. Relationships between HT and low-, intermediate-, and high-risk RS were compared with χ2 test. Kaplan-Meier curves were compared using log-rank test.
RESULTS.—
A total of 110 318 patients had RS testing. Of these, 23 220 (21%) had low, 70 822 (64.2%) intermediate, and 16 276 (14.8%) high RS. Histologic types were 80 476 (73%) ductal, 12 713 (11.5%) lobular, 12 449 (11.3%) mixed, 2151 (2%) mucinous, 610 (0.6%) tubular, 382 (0.4%) micropapillary, 365 (0.3%) salivary, 208 (0.2%) papillary, 49 (0.04%) medullary, 26 (0.02%) metaplastic, 26 (0.02%) neuroendocrine, and 863 (0.8%) unknown. The distribution of low-, intermediate-, and high-risk RS was significantly different among HTs. Higher percentages of high-risk RS were identified in patients with ductal, medullary, and metaplastic types (P < .001). The odds of having high-risk RS were lower for some HTs, including micropapillary, after multivariable adjustment (P < .05). The low number of estrogen receptor-positive medullary and metaplastic carcinomas tested had higher odds of having high-risk RS. In T1 and T2 tumors, when ductal, lobular, mixed, and other types combined were compared, the mortality was different.
CONCLUSIONS.—
This population-based study of RS in HTs showed high-risk RSs are identified in traditionally good prognostic subtypes. Micropapillary carcinoma has lower odds of high-risk RS even after multivariable adjustment.
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Papillary; Female; Humans; Prognosis; Risk Factors
PubMed: 34343231
DOI: 10.5858/arpa.2020-0837-OA -
World Journal of Gastroenterology Feb 2016The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a... (Review)
Review
The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.
Topics: Adenocarcinoma; Adult; Aged; Alcohol Drinking; Barrett Esophagus; Comorbidity; Disease Progression; Esophageal Neoplasms; Estrogen Replacement Therapy; Estrogens; Female; Gastroesophageal Reflux; Health Status Disparities; Humans; Incidence; Life Style; Male; Middle Aged; Obesity; Prevalence; Risk Assessment; Risk Factors; Sex Distribution; Sex Factors; Smoking
PubMed: 26855539
DOI: 10.3748/wjg.v22.i5.1800 -
International Journal of Clinical and... 2022Squamous cell transformation of the urinary bladder urothelium has various causes, symptoms, and few treatment options. The aim of this study was to analyze and compare...
OBJECTIVE
Squamous cell transformation of the urinary bladder urothelium has various causes, symptoms, and few treatment options. The aim of this study was to analyze and compare the expression of sex hormone receptors in non-keratinized and keratinized squamous metaplasia (NKSM, KSM), squamous cell carcinoma (SCC), and healthy urothelium with regard to possible therapeutic approaches.
METHODS
Biopsies from 26 patients with urothelial NKSM, KSM, and SCC were analyzed retrospectively. Tissue microarrays (TMA) of formalin-fixed paraffin-embedded (FFPE) bladder biopsies were stained with hematoxylin and eosin followed by immunohistochemical analysis with specific antibodies against estrogen, progesterone, and androgen receptors (ER, PR, AR) and assessment using the immunoreactive score. Statistical evaluations included the Wilcoxon signed-rank test and the Wilcoxon rank-sum test in the form of permutation tests.
RESULTS
Of the 15 women and 11 men included in this explorative study, 17 had metaplasia: 15 (six men, nine women) had NKSM and two KSM (both men). A total of nine patients (three men, six women) had keratinized SCC or urothelial carcinoma with squamous differentiation. The comparison between normal urothelial cells and metaplasia showed a significantly stronger expression in the metaplastic tissue (P=0.0374). The invasive carcinoma showed significantly less PR than the extracellular matrix of the healthy urothelium (P=0.0026). Expression of AR was nearly absent in healthy and metaplastic urothelium.
CONCLUSION
There appears to be an association between squamous metaplasia of the bladder mucosa and sex steroid hormone receptor expression, especially estrogen receptors. Topical hormone therapy should be considered.
PubMed: 35949808
DOI: No ID Found -
Breast Care (Basel, Switzerland) Dec 2022Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that accounts for 0.2-1% of all breast cancers. To date, there are only few institutional studies...
BACKGROUND
Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that accounts for 0.2-1% of all breast cancers. To date, there are only few institutional studies comparing survival rates between different subtypes. In this retrospective cohort study, we aim to evaluate factors effecting survival rates of different subtypes of MBC.
METHODS
This retrospective cohort study observed 118 nonmetastatic MBC patient records extracted from 15,244 breast cancer cases between December 2000 and December 2020. In order to analyze factors effecting survival rates of mesenchymal subtype of MBC, all cases are classified as mesenchymal ( = 45) and other ( = 48). Twenty-five cases could not be sub-classified due to the missing data. Univariate and multivariate logistic regression analyses were performed to define factors associated with survival rates.
RESULTS
Of the 15,244 cases, 118 (0.8%) were nonmetastatic MBC. 105 were triple negative and 12 were nonluminal HER2. There was no significant difference between mesenchymal and other subgroups for age, median tumor size, AJCC staging, and type of surgery. Of the five local recurrences with known subgroup, four of them had mesenchymal subtype. It is demonstrated that mesenchymal subtype was significantly associated with worse 5-year disease-free survival and disease-specific survival (HR: 2.35 [1.01-5.48], = 0.049, and HR: 3.16 [1.06-9.47], = 0.040 with 95% CI, respectively).
CONCLUSION
This study is one of the few studies presenting the survival outcomes of subtypes of MBCs. Nonetheless, it is the only study demonstrating that mesenchymal subtype had worse survival outcomes. Further studies are needed to determine the outcome of different subtypes of MBCs.
PubMed: 36590148
DOI: 10.1159/000525324