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Star-nosed moles
\"A photo-illustrated book for elementary readers about star-nosed moles. Readers learn about their underground habitat, feeding habits, their ultra-sensitive nose tentacles, and modes of survival. Includes fun facts, table of contents, glossary, further resources, and index\"-- Provided by publisher.
Book
Refined diagnosis of hydatidiform moles with p57 immunohistochemistry and molecular genotyping: updated analysis of a prospective series of 2217 cases
Immunohistochemical analysis of p57 expression and molecular genotyping accurately subclassify molar specimens into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and distinguish these from nonmolar specimens. Characteristics of a prospective series of potentially molar specimens analyzed in a large gynecologic pathology practice are summarized. Of 2217 cases (2160 uterine, 57 ectopic), 2080 (94%) were successfully classified: 571 CHMs (570 uterine, 1 ectopic), 498 PHMs (497 uterine, 1 ectopic), 900 nonmolar (including 147 trisomies, 19 digynic triploids, and 4 donor egg conceptions), and 56 androgenetic/biparental mosaics; 137 were complex or unsatisfactory and not definitively classified. CHMs dominated in patients aged < 21 and >45 years and were the only kind of molar conception found in the latter group. Of 564 successfully immunostained CHMs, 563 (99.8%) were p57-negative (1 p57-positive [retained maternal chromosome 11] androgenetic by genotyping). Of 153 genotyped CHMs, 148 (96.7%) were androgenetic (85% monospermic) and 5 were biparental, the latter likely familial biparental hydatidiform moles. Of 486 successfully immunostained PHMs, 481 (99%) were p57-positive (3 p57-negative [loss of maternal chromosome 11], 2 unknown mechanism). Of 497 genotyped PHMs, 484 (97%) were diandric triploid (99% dispermic) and 13 were triandric tetraploid (all at least dispermic). Of 56 androgenetic/biparental mosaics, 37 had a p57-negative complete molar component (16 confirmed as androgenetic by genotyping). p57 expression is highly correlated with genotyping, serving as a reliable marker for CHMs, and identifies molar components and androgenetic cell lines in mosaic conceptions. Correlation of morphology, p57 expression, genotyping data, and history are required to recognize familial biparental hydatidiform moles and donor egg conceptions, as the former can be misclassified as nonmolar and the latter can be misclassified as dispermic CHM on the basis of isolated genotyping results.
Journal Article
Carcinogenesis resistance in the longest‐lived rodent, the naked mole‐rat
Certain mammalian species are resistant to cancer, and a better understanding of how this cancer resistance arises could provide valuable insights for basic cancer research. Recent technological innovations in molecular biology have allowed the study of cancer‐resistant mammals, despite the fact that they are not the classical model animals, which are easily studied using genetic approaches. Naked mole‐rats (NMRs; Heterocephalus glaber) are the longest‐lived rodent, with a maximum lifespan of more than 37 years, and almost never show spontaneous carcinogenesis. NMRs are currently attracting much attention from aging and cancer researchers, and published studies on NMR have continued to increase over the past decade. Cancer development occurs via multiple steps and involves many biological processes. Recent research on the NMR as a model for cancer resistance suggests that they possess various unique carcinogenesis‐resistance mechanisms, including efficient DNA repair pathways, cell‐autonomous resistance to transformation, and dampened inflammatory response. Here, we summarize the molecular mechanisms of carcinogenesis resistance in NMR, which have been uncovered over the past two decades, and discuss future perspectives. The longest‐lived rodent, the naked mole‐rat has extraordinary resistance to carcinogenesis.
Journal Article
Hydatidiform Moles: Ancillary Techniques to Refine Diagnosis
Distinction of hydatidiform moles from nonmolar specimens and subclassification of hydatidiform moles as complete hydatidiform mole versus partial hydatidiform mole are important for clinical practice and investigational studies. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Diagnosis based on morphology is subject to interobserver variability and remains problematic, even for experienced gynecologic pathologists.
To explain how ancillary techniques target the unique genetic features of hydatidiform moles to establish diagnostic truth, highlight the issue of diagnostic reproducibility and importance of diagnostic accuracy, and illustrate use of p57 immunohistochemistry and polymerase chain reaction-based DNA genotyping for diagnosis.
Sources are the author's 10-year experience using ancillary techniques for the evaluation of potentially molar specimens in a large gynecologic pathology practice and the literature.
The unique genetics of complete hydatidiform moles (purely androgenetic), partial hydatidiform moles (diandric triploid), and nonmolar specimens (biparental, with allelic balance) allow for certain techniques, including immunohistochemical analysis of p57 expression (a paternally imprinted, maternally expressed gene) and genotyping, to refine diagnoses of hydatidiform moles. Although p57 immunostaining alone can identify complete hydatidiform moles, which lack p57 expression because of a lack of maternal DNA, this analysis does not distinguish partial hydatidiform moles from nonmolar specimens because both express p57 because of the presence of maternal DNA. Genotyping, which compares villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles, distinguishes purely androgenetic complete hydatidiform moles from diandric triploid partial hydatidiform moles, and both of these from biparental nonmolar specimens. An algorithmic approach to diagnosis using these techniques is advocated.
Journal Article
Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence
Cellular senescence is an important anticancer mechanism that restricts proliferation of damaged or premalignant cells. Cellular senescence also plays an important role in tissue remodeling during development. However, there is a trade-off associated with cellular senescence as senescent cells contribute to aging pathologies. The naked mole rat (NMR) (Heterocephalus glaber) is the longest-lived rodent that is resistant to a variety of age-related diseases. Remarkably, NMRs do not show aging phenotypes until very late stages of their lives. Here, we tested whether NMR cells undergo cellular senescence. We report that the NMR displays developmentally programmed cellular senescence in multiple tissues, including nail bed, skin dermis, hair follicle, and nasopharyngeal cavity. NMR cells also underwent cellular senescence when transfected with oncogenic Ras. In addition, cellular senescence was detected in NMR embryonic and skin fibroblasts subjected to γ-irradiation (IR). However, NMR cells required a higher dose of IR for induction of cellular senescence, and NMR fibroblasts were resistant to IR-induced apoptosis. Gene expression analyses of senescence-related changes demonstrated that, similar to mice, NMR cells up-regulated senescence-associated secretory phenotype genes but displayed more profound down-regulation of DNA metabolism, transcription, and translation than mouse cells. We conclude that the NMR displays the same types of cellular senescence found in a short-lived rodent.
Journal Article
Hydatidiform Moles: The Contribution of Ancillary Techniques in Refining Their Histopathological Diagnosis
A hydatidiform mole (HM) is the most common form of gestational trophoblastic disease (GTD). Differentiating hydatidiform moles (HMs) from non-molar pregnancies and distinguishing complete HMs (CHMs) from partial HMs (PHMs) remains challenging due to overlapping morphological features and a high rate of misclassification. This study aimed to evaluate reliable immunohistochemical markers for improving diagnostic accuracy and addressing the limitations of current molecular techniques. We retrospectively analyzed 64 cases of HMs and hydropic abortions (HAs), diagnosed in women aged 17–36 years between 2010 and 2024, at the Pathology Department of “Elena Doamna” Clinical Hospital, Iași, Romania. Routine histology was supplemented with immunohistochemistry (IHC) using p57, Ki-67, β-hCG, and E-cadherin, with semiquantitative immunoscores applied. Histology revealed 38 PHMs (59.37%), 16 CHMs (23.88%), and 10 HAs (15.62%). p57 was positive in 100% of PHMs and HAs but only in 18% of CHMs. Ki-67 expression was predominantly strong in CHMs, variable in PHMs, and weak in all HAs. β-hCG showed the highest expression in CHMs, followed by PHMs and HAs, while E-cadherin was strongest in HAs. Morphological features alone are insufficient for HM diagnosis; thus, ancillary techniques like p57 IHC and DNA genotyping are crucial to differentiate complete, partial moles, and non-molar specimens by revealing unique genetic patterns, especially p57 absence in CHMs and ploidy/parental origin in PHMs. In this context, an algorithmic approach integrating histology, immunohistochemistry, and genotyping reduces interobserver variability and refines diagnostic precision.
Journal Article
Pathogenic role of Twist-1 protein in hydatidiform molar pregnancies and investigation of its potential diagnostic utility in complete moles
Background
Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary.
Methods
In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score.
Results
Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p < 0.001). Moderate to strong staining intensity in more than 50% of villous stromal cells, can differentiate CM and PM with 89.5% sensitivity and 75% specificity. In syncytiotrophoblasts of CM, Twist-1 expression was significantly lower than PM (p < 0.001). Negative or weak staining intensity in less than 10% of syncytiotrophoblasts, can distinguish CM and PM with 82.9% sensitivity and 60% specificity.
Conclusion
A higher expression of Twist-1 in villous stromal cells of hydatidiform moles is a sensitive and specific marker for the diagnosis of CMs. An elevated expression of this marker in villous stromal cells suggests another pathogenic mechanism for more aggressiveness of CMs in addition to the characteristics of trophoblast cells. The opposite result was obtained in the expression of Twist-1 in the syncytiotrophoblasts, compatible with defects in the process of formation of these supportive cells in CMs.
Journal Article
Combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios for early prediction of postmolar gestational trophoblastic neoplasia
PurposeTo investigate factors predicting postmolar gestational trophoblastic neoplasia (GTN) by combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios.MethodsThis retrospective study enrolled patients with histopathologically proven molar pregnancy. Patients lost to follow-up before remission or developing postmolar GTN were excluded. Demographic and clinical characteristics and hCG data obtained before and after molar evacuation were collected. Area under the receiver operating characteristic curve (AUC) analysis was used to identify the hCG and hCG ratio cutoff values that predict postmolar GTN. Multivariate analysis was employed to identify independent predictors of GTN.ResultsThere were 113 complete moles, 11 partial moles, and 52 unspecified moles included in the final analysis. Of the 176 cases, 90 achieved remission and 86 developed post-molar GTN. The incidence of postmolar GTN was 48.9%, with a median time to GTN development of 5 weeks. Univariate analysis showed age, molar evacuation performed elsewhere, pre-evacuation hCG, hCG at 2nd week post-evacuation, and ratio of hCG at 2nd week post-evacuation to post-evacuation hCG significantly predict GTN. Multivariate analysis revealed an hCG value ≥ 1400 IU/L at 2nd week post-evacuation (AUC: 0.92, aOR: 6.51, 95% CI 1.28–33.16; p = 0.024) and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 (AUC: 0.88, aOR: 12.27, 95% CI 2.15–70.13; p = 0.005) to independently predict GTN.ConclusionsAn hCG value ≥ 1400 IU/L at 2nd week post-evacuation and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 independently and reliably predict postmolar GTN.
Journal Article
Morphology combined with HER2 D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping
AimsA hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by HER2 dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.MethodsOver a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of HER2 D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus.ResultsThirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases.ConclusionsThis study validates the use of HER2 D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.
Journal Article
Ethnic disparities in complete and partial molar pregnancy incidence: a retrospective analysis of arab and jewish women in single medical center
Background
Molar pregnancies, encompassing complete and partial moles, represent a rare and enigmatic gestational disorder with potential ethnic variations in incidence. This study aimed to investigate relations of ethnicity with risks of complete and partial molar pregnancies within an Israeli population while accounting for age differences.
Methods
A retrospective study was conducted of data recorded during 2007–2021 in an academic medical center in Israel. The study population comprised 167 women diagnosed with complete or partial moles, for whom data were obtained through histological examination and P57 immunostaining. Maternal age and ethnicity were extracted from electronic medical records. Incidence rates were calculated per 10,000 live births, and a nested case-control study compared demographic characteristics and molar pregnancy incidences between Arab and Jewish women. Statistical analyses included age-adjusted comparisons, relative risk calculations and multivariate logistic regression.
Results
The overall risk of molar pregnancy was 22 per 10,000 live births (95% confidence interval [CI] 18–25). Among Arab women, the overall risk was 21 (95% CI 17–25), and for PM and CM: 14 (95% CI 11–17) and 7 (95% CI 5–10), respectively. Among Jewish women, the overall risk was 23 (95% CI 18–29), and for PM and CM: 12 (95% CI 8–17) and 11 (95% CI 7–16), respectively. Among Arab women compared to Jewish women, the proportion of all the partial moles was higher: (65.3% vs. 51.6%,
p
= 0.05). The incidence of partial mole was higher among Arab than Jewish women, aged 35–39 years (26 vs. 8 per 10,000,
p
= 0.041), and did not differ in other age groups. After adjusting for age, the relative risk of partial moles was lower among Jews than Arabs (0.7, 95% CI 0.4-1.0,
p
= 0.053). For Arab compared to Jewish women, the mean age at molar pregnancies was younger: 31.0 vs. 35.1 years. However, other factors did not differ significantly between Arab and Jewish women with molar pregnancies. In multivariate analysis, Jewish ethnicity was significantly associated with a higher risk of complete molar pregnancies (OR = 2.19, 95% CI 1.09–4.41,
p
= 0.028).
Conclusion
This study highlights ethnic differences in molar pregnancy risk within the Israeli population. Jewish ethnicity was associated with a higher risk of complete molar pregnancies, while Arab women had a significantly higher risk of partial moles. These findings underscore the need to consider ethnicity when studying gestational disorders. Further research should seek to elucidate the underlying factors contributing to these differences.
Journal Article