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Computational and Structural... 2022Cox proportional hazard regression (CPH) model relies on the proportional hazard (PH) assumption: the hazard of variables is independent of time. CPH has been widely...
BACKGROUND
Cox proportional hazard regression (CPH) model relies on the proportional hazard (PH) assumption: the hazard of variables is independent of time. CPH has been widely used to identify prognostic markers of the transcriptome. However, the comprehensive investigation on PH assumption in transcriptomic data has lacked.
RESULTS
The whole transcriptomic data of the 9,056 patients from 32 cohorts of The Cancer Genome Atlas and the 3 lung cancer cohorts from Gene Expression Omnibus were collected to construct CPH model for each gene separately for fitting the overall survival. An average of 8.5% gene CPH models violated the PH assumption in TCGA pan-cancer cohorts. In the gene interaction networks, both hub and non-hub genes in CPH models were likely to have non-proportional hazards. Violations of PH assumption for the same gene models were not consistent in 5 non-small cell lung cancer datasets (all kappa coefficients < 0.2), indicating that the non-proportionality of gene CPH models depended on the datasets. Furthermore, the introduction of log(t) or sqrt(t) time-functions into CPH improved the performance of gene models on overall survival fitting in most tumors. The time-dependent CPH changed the significance of log hazard ratio of the 31.9% gene variables.
CONCLUSIONS
Our analysis resulted that non-proportional hazards should not be ignored in transcriptomic data. Introducing time interaction term ameliorated performance and interpretability of non-proportional hazards of transcriptome data in CPH.
PubMed: 35070171
DOI: 10.1016/j.csbj.2022.01.004 -
Caspian Journal of Internal Medicine 2021Mucinous cystadenocarcinoma is a relatively uncommon histological subtype of breast cancer that is a cystic form of papillary mucinous carcinoma. It is regularly...
BACKGROUND
Mucinous cystadenocarcinoma is a relatively uncommon histological subtype of breast cancer that is a cystic form of papillary mucinous carcinoma. It is regularly negative for estrogen and progesterone receptors and it is most often diagnosed in older than 55-60 years old. The incidence of breast mucinous cystadenocarcinoma is about 1-6% of primary breast cancers. Here, we present a case of breast mucinous cystadenocarcinoma of left breast in a 69-year-old female which is positive for estrogen and progesterone receptors.
CASE PRESENTATION
In this article, we describe a case of a-69-year-old female with a painful mass in her left breast. Based on intraoperative pathology consult, neoplastic tissue mostly floating in mucinous lakes with invasion to surrounding stroma was seen. Immunohistochemistry profile showed positive estrogen and progesterone receptors and negative for HER2.
CONCLUSION
Mucinous cystadenocarcinoma of breast is typically triple negative for hormone receptors. But ER and PR positive variant of this tumor is rare, giving the chance of a better prognosis for the patient with hormonal therapy.
PubMed: 34760102
DOI: 10.22088/cjim.12.0.444 -
Virchows Archiv : An International... Jan 2022Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal... (Review)
Review
Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal carcinoma in situ (DCIS) or lobular neoplasia, papillary DCIS, encapsulated papillary carcinomas without or with invasion, solid papillary carcinomas, and invasive papillary carcinomas. A micropapillary pattern characterized by lack of fibrous stalks within the papillae is observed in micropapillary DCIS and invasive micropapillary carcinoma. In addition, a variety of other rare breast lesions reveals a papillary architecture such as tall cell carcinoma with reversed polarity (TCCRP) and mucinous cystadenocarcinoma, adenomyoepithelioma, and secretory carcinoma. In addition, benign lesions such as usual ductal hyperplasia, apocrine metaplasia, gynecomastia, and juvenile papillomatosis may show a papillary or micropapillary architecture. Fragments of a benign papilloma in a breast biopsy are considered a lesion of uncertain malignant potential (B3 in the European classification) and excision is mostly recommended. Although the knowledge about molecular pathology of papillary breast lesions has increased, there is not sufficient evidence for diagnostically useful molecular features, yet. The aim of this review is to provide an update on papillary and micropapillary lesions with emphasis on problematic areas for daily diagnostic work including biopsies.
Topics: Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Humans; Male; Papilloma
PubMed: 34734332
DOI: 10.1007/s00428-021-03182-7 -
In Vivo (Athens, Greece) 2021We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma.
BACKGROUND/AIM
We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
CASE REPORT
A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA.
CONCLUSION
Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.
Topics: Adenocarcinoma; Carcinoma in Situ; Cystadenocarcinoma, Serous; Diagnostic Errors; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Ovarian Neoplasms
PubMed: 34697203
DOI: 10.21873/invivo.12667 -
Journal of Ovarian Research Oct 2021Mixed cell ovarian adenocarcinoma (MCOA) is a malignant gynecologic tumor consisting of serous, mucous, and papillary tumor cells. However, the clinical features and...
BACKGROUND
Mixed cell ovarian adenocarcinoma (MCOA) is a malignant gynecologic tumor consisting of serous, mucous, and papillary tumor cells. However, the clinical features and prognosis of MCOA patients are unclear.
METHODS
In this study, univariate and multivariate Cox proportional risk models were performed to identify independent prognostic factors. The Kaplan-Meier method was used to assess the relationship between clinical characteristics and patient survival. Finally, a nomogram was constructed and validated to predict patient survival time, and the C-index was used to evaluate the efficacy of the nomogram.
RESULTS
A total of 2,818 patients diagnosed with MCOA were identified, and the 5-year survival rate was 62%. Univariate and multivariate Cox models suggested that age (HR=1.28, 95% CI[1.15,1.44]), grade (HR=1.26, 95% CI[1.12,1.41]), SEER stage (HR=1.63, 95% CI[1.25,2.13]) and AJCC (American Joint Committee on Cancer) stage (HR=1.59, 95% CI[1.36,1.86]) were independent prognostic factors for MCOA patients. After propensity score matching for age, grade, SEER stage, and AJCC stage, the 5-year survival rate was 69.7% for ovarian serous cystadenocarcinoma and 62.9% for ovarian papillary serous cystadenocarcinoma. These results mean that serous adenocarcinoma had the best prognosis of the three pathologic types of ovarian carcinoma (p<0.0001), with no significant difference between papillary serous cystadenocarcinoma and MCOA (p=0.712). Finally, a nomogram consisting of age, grade, SEER stage, and AJCC stage was established and validated to predict the survival time, with C-indices of 0.743 and 0.731, respectively.
CONCLUSIONS
In summary, MCOA is uncommon, and age, grade, SEER stage, and AJCC stage are independent prognostic factors. Compared with other common malignant ovarian tumors, MCOA has a poor prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cystadenocarcinoma, Serous; Female; Humans; Middle Aged; Nomograms; Ovarian Neoplasms; Prognosis; Young Adult
PubMed: 34674727
DOI: 10.1186/s13048-021-00896-9 -
Computational and Structural... 2021Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.
BACKGROUND
Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.
METHODS
Weighted gene co-expression network analysis was used to identify meaningful macrophage-related gene genes for clustering. Pamr, SVM, and neural network were applied for validating clustering results. Somatic mutation and methylation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of MScores. The expression of macrophage-specific genes were evaluated in tumor microenvironment based on single cell sequencing analysis. A total of 2365 samples from 15 glioma datasets and 5842 pan-cancer samples were used for external validation of MScore.
RESULTS
Macrophages were identified to be negatively associated with the survival of glioma patients. Twenty-six macrophage-specific DEGs obtained by elastic regression and PCA were highly expressed in macrophages at single-cell level. The prognostic value of MScores in glioma was validated by the active proinflammatory and metabolic profile of infiltrating microenvironment and response to immunotherapies of samples with this signature. MScores managed to stratify patient survival probabilities in 15 external glioma datasets and pan-cancer datasets, which predicted worse survival outcome. Sequencing data and immunohistochemistry of Xiangya glioma cohort confirmed the prognostic value of MScores. A prognostic model based on MScores demonstrated high accuracy rate.
CONCLUSION
Our findings strongly support a modulatory role of macrophages, especially M2 macrophages in glioma progression and warrants further experimental studies.
PubMed: 34471502
DOI: 10.1016/j.csbj.2021.08.019 -
Medicine and Pharmacy Reports Jul 2021Mucinous cystic neoplasms of the liver (MCN-L, (previously referred to as cystadenomas or cystadenocarcinoma) are rare cystic tumors that occur within the liver...
Mucinous cystic neoplasms of the liver (MCN-L, (previously referred to as cystadenomas or cystadenocarcinoma) are rare cystic tumors that occur within the liver parenchyma, or less frequently, in the extrahepatic bile ducts. They are reported to account for <5% of all liver cysts. The differential diagnosis of MCN-L includes intraductal papillary neoplasm of the bile duct (IPNB), intrahepatic cholangiocarcinoma with cystic change, echinococcal cyst, and a simple cyst. Invasive MCNs can only be differentiated from non-invasive MCNs by microscopic evaluation for the presence of ovarian-type stroma. Intraoperative biopsy and frozen section(s) are essential to differentiate MCNs from other cystic liver lesions. The treatment of choice is complete excision and can result in excellent survival with initial correct diagnosis. But its rare presentation and insufficient recognition frequently lead to an incorrect initial or delayed diagnosis or misdiagnosis.
PubMed: 34430860
DOI: 10.15386/mpr-1543 -
Medicina (Kaunas, Lithuania) Apr 2021The possible presence of malignant adnexal mass should be considered during pregnancy. For this reason, it is important to keep in mind such possibility while performing...
BACKGROUND
The possible presence of malignant adnexal mass should be considered during pregnancy. For this reason, it is important to keep in mind such possibility while performing routine obstetric ultrasounds to diagnose asymptomatic ovarian cancer in the early stages.
CASE PRESENTATION
27-year-old pregnant patient with a known adnexal tumour occurring at week 20 and enlarged supraclavicular lymph nodes of 3 cm size who was diagnosed with metastases from low-grade papillary serous ovarian carcinoma. The patient, obstetricians, neonatologists and oncologists agreed on initiating neoadjuvant chemotherapy and performing an elective C-section at week 34. She gave birth to a female infant weighing 2040 g who is currently in good health, and continues receiving follow-up care by a medical oncologist.
CONCLUSIONS
An early diagnosis of gynaecologic malignancies during pregnancy is of critical importance because, although they are very rare, managing and treating carcinomas at an early stage allow us to increase maternal and fetal well-being and to offer more alternatives to our patients.
Topics: Adult; Carcinoma; Cystadenocarcinoma, Serous; Female; Humans; Lymph Nodes; Neoadjuvant Therapy; Ovarian Neoplasms; Pregnancy
PubMed: 33924942
DOI: 10.3390/medicina57050426 -
Diagnostics (Basel, Switzerland) Apr 2021Ovarian cancer remains a major diagnostic and therapeutic problem in modern gynecological oncology. For this reason, research which focuses on the search for new...
Ovarian cancer remains a major diagnostic and therapeutic problem in modern gynecological oncology. For this reason, research which focuses on the search for new diagnostic markers and the assessment of their possible usefulness in clinical practice is still being conducted. The aim of this study was to evaluate serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer. Patients with ovarian serous cystadenoma () and papillary serous cystadenocarcinoma () were included in the study, as well as healthy women who constituted the control group. The results of the study revealed a statistically significantly decreased mean serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer as compared to the control group ( ˂ 0.001), which indicates the involvement of the studied parameters in immune system disturbances occurring in the process of apoptosis by the extrinsic and intrinsic pathway and may be one of the mechanisms of immunosuppression accompanying these tumors. Determination of serum levels of examined caspases and CA 125 antigen in women with ovarian cancer in combination with other markers may prove useful in the future in the diagnosis of ovarian cancer, but this requires further studies.
PubMed: 33919909
DOI: 10.3390/diagnostics11040704 -
Porcine Health Management Apr 2021The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport...
BACKGROUND
The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport a Escorxadors [SESC] IRTA-CReSA]) from slaughtered pigs from 1998 to 2018 (April) in Catalonia (Spain). The aim of the study was to describe the spectrum of spontaneous neoplastic lesions found in slaughtered pigs and to compare the reported tumor cases with previous published data. Lymphoid neoplasms were characterized and classified using the WHO classification adapted for animals.
RESULTS
The most reported neoplasm during this period was lymphoma (28). Within lymphomas, the B-cell type was the most common, being the diffuse large B-cell lymphoma (15/28) the most represented subtype. Other submitted non-lymphoid neoplasms included melanoma (7), nephroblastoma (3), mast cell tumor (2), liposarcoma (2), osteochondromatosis (2), papillary cystadenocarcinoma (1), peripheral nerve sheath tumor (1), lymphoid leukemia (1), fibropapilloma (1), hemangiosarcoma (1), hepatoma (1), histiocytic sarcoma (1), pheochromocytoma (1) and osteosarcoma (1).
CONCLUSIONS
The existence of a well-established Slaughterhouse Support Network allowed the compilation of comprehensive data for further epidemiological and pathological studies, particularly about less commonly reported lesions in livestock such as neoplasms in pigs.
PubMed: 33827694
DOI: 10.1186/s40813-021-00207-0