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The American Journal of Surgical... Feb 2018We sought to classify endocervical adenocarcinomas (ECAs) based on morphologic features linked to etiology (ie, human papillomavirus [HPV] infection), unlike the World...
We sought to classify endocervical adenocarcinomas (ECAs) based on morphologic features linked to etiology (ie, human papillomavirus [HPV] infection), unlike the World Health Organization 2014 classification. The International Endocervical Adenocarcinoma Criteria and Classification (IECC criteria), described herein, distinguishes between human papillomavirus-associated adenocarcinoma (HPVA), recognized by the presence of luminal mitoses and apoptosis seen at scanning magnification, and no or limited HPVA features (nonhuman papillomavirus-associated adenocarcinoma [NHPVA]). HPVAs were then subcategorized based on cytoplasmic features (mostly to provide continuity with preexisting classification schemes), whereas NHPVAs were subclassified based on established criteria (ie, gastric-type, clear cell, etc.). Complete slide sets from 409 cases were collected from 7 institutions worldwide. Tissue microarrays representing 297 cases were constructed; immunohistochemistry (p16, p53, vimentin, progesterone receptor) and chromogenic in situ hybridization using an RNA-based probe set that recognizes 18 varieties of high-risk HPV were performed to validate IECC diagnoses. The 5 most common IECC diagnoses were usual-type (HPVA) (73% of cohort), gastric-type (NHPVA) (10%), mucinous adenocarcinoma of HPVA type, including intestinal, mucinous not otherwise specified, signet-ring, and invasive stratified mucin-producing carcinoma categories (9%), clear cell carcinoma (NHPVA) (3%) and adenocarcinoma, not otherwise specified (2%). Only 3 endometrioid carcinomas were recognized and all were NHPVA. When excluding cases thought to have suboptimal tissue processing, 90% and 95% of usual-type IECC cases overexpressed p16 and were HPV, whereas 37% and 3% of NHPVAs were p16 and HPV, respectively. The 1 HPV gastric-type carcinoma was found to have hybrid HPVA/NHPVA features on secondary review. NHPVA tumors were larger and occurred in significantly older patients, compared with HPVA tumors (P<0.001). The high-risk HPV chromogenic in situ hybridization probe set had superior sensitivity, specificity, and positive and negative predictive values (0.955, 0.968, 0.992, 0.833, respectively) compared with p16 immunohistochemistry (0.872, 0.632, 0.907, 0.545, respectively) to identify HPV-related usual carcinoma and mucinous carcinoma. IECC reliably segregates ECAs into HPVA and NHPVA types using morphology alone. This study confirms that usual-type ECAs are the most common type worldwide and that mucinous carcinomas comprise a mixture of HPVA and NHPVA, with gastric-type carcinoma being the major NHPVA type. Endometrioid and serous carcinomas of the endocervix are extraordinarily rare. Should clinical outcomes and genomic studies continue to support these findings, we recommend replacement of the World Health Organization 2014 criteria with the IECC 2017.
Topics: Adenocarcinoma; Biomarkers, Tumor; Consensus; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; In Situ Hybridization; Neoplasm Invasiveness; Papillomaviridae; Papillomavirus Infections; Predictive Value of Tests; RNA, Viral; Terminology as Topic; Tissue Array Analysis; Uterine Cervical Neoplasms
PubMed: 29135516
DOI: 10.1097/PAS.0000000000000986 -
The American Journal of Surgical... Apr 2021Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly...
Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly understood. Although their morphologic, immunohistochemical, and molecular profiles have been recently defined, little is known about their clinical behavior. Small studies have demonstrated inconsistent findings and no large studies have examined the clinical behavior of these adenocarcinomas. In this multi-institutional study, representing the largest and most stringently defined cohort of cases to date, we examined the clinicopathologic features of 99 MAs and MLAs (30 MAs of the uterine cervix, 44 MLAs of the endometrium, and 25 MLAs of the ovary). Only tumors with characteristic mesonephric morphology and either immunohistochemical or molecular support were included. Our results demonstrate that the majority of mesonephric neoplasms presented at an advanced stage (II to IV) (15/25 [60%] MA of the cervix, 25/43 [58%] MLA of the endometrium, and 7/18 [39%] MLA of the ovary). The majority (46/89 [52%] overall, 12/24 [50%] MA of the cervix, 24/41 [59%] MLA of the endometrium, and 10/24 [42%] MLA of the ovary) developed recurrences, most commonly distant (9/12 [75%] MA of the cervix, 22/24 [92%] MLA of the endometrium, and 5/9 [56%] MLA of the ovary). The 5-year disease-specific survival was 74% (n=26) for MA of cervix, 72% (n=43) for MLA of endometrium, and 71% (n=23) for MLA of ovary. Our results confirm that mesonephric neoplasms are a clinically aggressive group of gynecologic carcinomas that typically present at an advanced stage, with a predilection for pulmonary recurrence.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Databases, Factual; Endometrial Neoplasms; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; North America; Northern Ireland; Ovarian Neoplasms; Progression-Free Survival; Registries; Time Factors; Uterine Cervical Neoplasms; Wolffian Ducts
PubMed: 33165093
DOI: 10.1097/PAS.0000000000001612 -
Archives of Pathology & Laboratory... Mar 2007Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these... (Review)
Review
CONTEXT
Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these specimens.
OBJECTIVE
To emphasize practical aspects of endometrial specimen handling and reporting, with selected comments on common diagnostic pitfalls, including (1) the diagnosis of endometrial intraepithelial carcinoma in atrophic endometrial biopsy specimens, (2) evaluation of adequacy of endometrial sampling specimens, (3) problems in diagnosing and measuring the depth of myometrial invasion in endometrial carcinoma, (4) the question of metastasis versus independent primaries in concurrent carcinomas of endometrium and one or both ovaries, (5) the problematic differential diagnoses between type 1 (primarily endometrioid) and type 2 (primarily serous) adenocarcinomas, and (6) atypical hyperplasia and proposed classification systems for its replacement.
DATA SOURCES
Published literature, consensus statements, and personal experience.
CONCLUSIONS
A systematic approach to the handling and reporting of endometrial specimens reduces the potential for omission and error. Recognition of diagnostic pitfalls and practical approaches to their resolution help improve quality.
Topics: Adenocarcinoma; Biopsy; Carcinoma, Endometrioid; Diagnosis, Differential; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Hysterectomy; Myometrium; Pathology, Clinical
PubMed: 17516740
DOI: 10.5858/2007-131-372-TE -
Cell Death & Disease Dec 2022Endometrial cancer is a common gynecological malignancy. With the onset of EC patients younger, conservative treatment with progesterone has become an important option...
Endometrial cancer is a common gynecological malignancy. With the onset of EC patients younger, conservative treatment with progesterone has become an important option for patients trying to preserve reproductive function. However, progesterone resistance is a key factor affecting the efficacy of therapy and it is urgent to clarify the mechanism so as to propose a potential target and inhibit the development of endometrial adenocarcinoma and progesterone resistance. MGLL, an important factor involved in lipid mobilization, is overexpressed in many tumors, however the biological function of MGLL in the development of endometrial adenocarcinoma and the process of progesterone resistance still remains unclear. In this study, we first found MGLL was highly expressed in progesterone resistant samples of endometrial adenocarcinoma, and then we verified its expression was increased in endometrial adenocarcinoma. Through in vitro and in vivo experiments, we demonstrated that overexpression of MGLL promoted tumor proliferation, metastasis and the occurrence of progestogen resistance, knockdown MGLL inhibited tumor proliferation, metastasis and reversed progestogen resistance. In addition, knockdown of MGLL can sensitize endometrial adenocarcinoma cells to progesterone, possibly by affecting ROS generation and reducing the expression of AKR1C1. Finally, it was verified that ABX-1431, MGLL inhibitor, reversed progesterone resistance and enhanced the sensitivity of endometrial adenocarcinoma to progesterone both in vitro and in vivo. In conclusion, the high expression of MGLL is involved in the occurrence and development of endometrial adenocarcinoma and progesterone resistance. Targeted inhibition of MGLL by inhibitors may be an effective method for the treatment of progesterone resistance in endometrial adenocarcinoma.
Topics: Female; Humans; Progesterone; Progestins; Uterine Neoplasms; Endometrial Neoplasms; Receptors, Progesterone; Adenocarcinoma
PubMed: 36550099
DOI: 10.1038/s41419-022-05507-z -
Modern Pathology : An Official Journal... Jan 2016Endocervical adenocarcinomas can be classified into two main types of tumors, namely, those related to high-risk human papillomavirus and those unrelated to high-risk... (Review)
Review
Endocervical adenocarcinomas can be classified into two main types of tumors, namely, those related to high-risk human papillomavirus and those unrelated to high-risk human papillomavirus. The former, representing the vast majority, are referred to as endocervical adenocarcinomas of usual type and the latter are dominated by the gastric-type mucinous adenocarcinomas. Commonly encountered diagnostic problems concerning these endocervical adenocarcinomas include: (1) diagnosing invasion for endocervical adenocarcinomas of usual type, particularly superficial forms which must be distinguished from extensive endocervical adenocarcinoma in situ; (2) distinguishing high-risk human papillomavirus-related endocervical adenocarcinomas from endometrial endometrioid carcinomas; and (3) distinguishing benign/hyperplastic mucinous endocervical glandular proliferations from gastric-type mucinous endocervical adenocarcinomas, particularly minimal deviation adenocarcinoma. The current review provides practical points and numerous illustrative examples to guide pathologists in addressing these diagnostic challenges in routine practice.
Topics: Adenocarcinoma; Diagnosis, Differential; Female; Humans; Papillomavirus Infections; Uterine Cervical Neoplasms
PubMed: 26715171
DOI: 10.1038/modpathol.2015.131 -
The International Journal of Biological... Jan 2018Human chorionic gonadotropin (hCG) is a peptide hormone which plays an important role during pregnancy. But its impact is not limited to pregnancy; it also influences... (Review)
Review
Human chorionic gonadotropin (hCG) is a peptide hormone which plays an important role during pregnancy. But its impact is not limited to pregnancy; it also influences tumor formation and metastatic outgrowth, especially in endometrial adenocarcinoma and breast cancer. This review summarizes what has been written in the literature about the role of hCG as a tumor marker in these 2 gynecological malignancies and also about the signal transduction pathways in which hCG is involved. HCG can, on the one hand, be a marker for the progression of a malignant disease, and on the other hand, it may be a point for therapeutical intervention, so further research into this molecule would be very much worthwhile.
Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Chorionic Gonadotropin; Endometrial Neoplasms; Female; Humans
PubMed: 28967068
DOI: 10.5301/ijbm.5000290 -
International Journal of Gynaecology... Oct 2021This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health... (Review)
Review
This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health Organization Classification of Female Genital Tract Tumours, published in 2020. Topics include the compelling evidence that a large majority of extrauterine high-grade serous carcinomas arise from the fallopian tube; the Cancer Genome Atlas (TCGA) Classification of endometrial carcinomas; the discovery that most so-called synchronous endometrial and ovarian endometrioid carcinomas represent metastasis from the endometrium to the ovary; and the division of cervical, vaginal, and vulval carcinomas into clinically meaningful HPV-associated and HPV-independent types. Newly described tumor types are covered, including endometrial and ovarian mesonephric-like adenocarcinoma, uterine sarcoma types associated with specific molecular abnormalities, and gastric (gastrointestinal)-type adenocarcinomas of the endometrium and vagina. Important molecular events in ovarian sex cord-stromal tumors are also discussed.
Topics: Adenocarcinoma; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Ovarian Neoplasms; Uterine Neoplasms
PubMed: 34669206
DOI: 10.1002/ijgo.13871 -
Archives of Pathology & Laboratory... Dec 2017- Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal,... (Review)
Review
CONTEXT
- Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge.
OBJECTIVE
- To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas. The paper presents a concise summary of the issues that may be particularly difficult in histopathologic diagnosis, such as differentiating neoplastic lesions from benign mimics, determining the tumor type, differentiating early invasive lesions from adenocarcinoma in situ, measuring the depth of invasion, and, finally, differentiating primary cervical adenocarcinoma from uterine endometrioid adenocarcinoma and tumors metastatic from other primary sites.
DATA SOURCES
- The study employed a PubMed search of recently published reports.
CONCLUSIONS
- Early detection of HPV-positive tumor types may be aided with the expansion of HPV testing; however, early diagnosis of HPV-negative cervical adenocarcinomas will continue to pose a challenge and may require the development of additional molecular testing techniques.
Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Early Detection of Cancer; Endometrial Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms
PubMed: 28644686
DOI: 10.5858/arpa.2016-0356-RA -
Oncology Reports May 2020Endometrial adenocarcinoma is one of the most common types of gynecological malignancies and its incidence and mortality rates are increasing. Due to tumor recurrence...
Endometrial adenocarcinoma is one of the most common types of gynecological malignancies and its incidence and mortality rates are increasing. Due to tumor recurrence and metastasis, the overall five‑year survival rate of patients with endometrial adenocarcinoma is shortened. The aim of the present was to investigate the role of the polycomb group protein B‑lymphoma Mo‑MLV insertion region 1 (BMI‑1) in the invasion, metastasis and the epithelial‑mesenchymal transition (EMT) of endometrial adenocarcinoma cells, as well its effects on the prognosis of patients with endometrial adenocarcinoma. Immunohistochemistry was used to examine the expression profile of BMI‑1 in normal and endometrial adenocarcinoma tissues. Western blotting was used to examine the expression levels of BMI‑1 and EMT markers. Kaplan‑Meier plots and a Cox proportional hazards model were used to assess the overall survival. MTT cell viability assays were used to detect the proliferation of endometrial cancer cells. Transwell assays were used to examine cell migration and invasion. Small interfering RNA was used to downregulate BMI‑1 expression levels, to study its effect on EMT. Immunohistochemical and clinicopathological analyses showed that BMI‑1 expression was increased in endometrial adenocarcinoma tissue compared with the normal endometrial tissue (P<0.05). The increased expression levels of BMI‑1 were closely associated with stage, myometrial invasion and lymph node metastasis (P<0.05). Kaplan‑Meier plots and a Cox proportional hazards model showed that increased BMI‑1 expression was associated with a less favorable prognosis [P=0.040, hazards ratio (HR)=1.596] and was associated with late‑stage adenocarcinoma (P=0.006, HR=1.670). Myometrial invasion (P=0.006, HR=1.509) and lymph node metastasis (P=0.004, HR=1.703) were determined to predict a less favorable prognosis. Downregulation of BMI‑1 reduced migration and invasion in endometrial cancer cells in vivo. It was also found that downregulation of BMI‑1 increased the expression levels of the epithelial markers E‑cadherin and keratin, and decreased the expression levels of the mesenchymal markers N‑cadherin, vimentin and the downstream transcription factor, Slug. In conclusion, BMI‑1 expression was correlated with tumor invasion and metastasis, contributing to deep myometrial invasion and lymph node metastasis, and was a poor prognostic factor for endometrial adenocarcinoma.
Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Polycomb Repressive Complex 1; Prognosis; RNA, Small Interfering; Up-Regulation
PubMed: 32323819
DOI: 10.3892/or.2020.7539 -
BioMed Research International 2021Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal...
Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d'origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma . This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.
Topics: Adenocarcinoma; Animals; Carcinogens; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Receptor Protein-Tyrosine Kinases; Signal Transduction; Smad Proteins; Xenograft Model Antitumor Assays; Mice
PubMed: 34712728
DOI: 10.1155/2021/2282916