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At least 19 recordsLinked to original sources

A Study on Differential Proteomics in Differentiated Gastric Adenocarcinoma With Low-grade Atypia Based on Paraffin-embedded Tissues.

In this study, we analyzed and characterized differentially expressed proteins in differentiated gastric adenocarcinoma with low-grade atypia for screening potential protein markers. We collected gastric tissue specimens from 90 patients treated at the Pathology Department of the First People's Hospital of Yunnan Province, China, between January 2019 and December 2022. These specimens had been fixed in 10% neutral-buffered formalin and embedded in paraffin. We classified these samples into 3 groups: the control group (normal gastric mucosa), the low-grade atypia group (differentiated gastric adenocarcinoma with low-grade atypia), and the high-grade atypia group (differentiated gastric adenocarcinoma with high-grade atypia), consisting of 30 cases in each group. We analyzed differential proteomes with the data-independent acquisition-mass spectrometry (DIA-MS) methodology and selected 4 differentially expressed proteins that were subjected to immunohistochemistry (IHC) staining for validation. A total of 4406 proteins were identified, among which 598 and 357 proteins were statistically different in the low-grade atypia group as compared with the control group and the high-grade atypia group, respectively. IHC staining showed that the expression of FHL3, CSRP2, and FCGR3A was significantly higher in the low-grade atypia group than in the control group ( P <0.05) and significantly higher in the high-grade atypia group than in the low-grade atypia group ( P <0.05). FHL2 expression was negative to weakly positive in the control and low-grade atypia groups and not significantly different between the 2 groups, whereas FHL2 expression in the high-grade atypia group was significantly higher than in the control and low-grade atypia groups ( P <0.05). Proteomic analysis is helpful for discovering new protein markers. Using a combination of FHL3, CSRP2, and FCGR3A can increase the accuracy of the pathologic diagnosis of differentiated gastric adenocarcinoma with low-grade atypia.

Humans

Incidence of epithelial atypia in radicular cysts: a preliminary investigation.

Histologic sections of 100 radicular cysts were scored for epithelial atypia, inflammation, and presence of other histologic features. No atypia was found in 32 cases. In 34 cases, atypia occurred in epithelium that was heavily infiltrated with chronic inflammatory cells. There were 26 cases of slight atypia, six cases of moderate atypia, one case of severe atypia, and one case that appeared to be carcinoma arising in a cyst wall. There was no evidence that inflammation in the connective tissues occurred more frequently or was more severe in cases that exhibited greater degrees of atypia.

Aged

Epithelial atypias associated with intrauterine contraceptive devices (IUD).

A total of 99 gynecologic smears with atypical cells from 74 patients wearing IUDs was reviewed. Endometrial and cervical tissues were examined. The cases were categorized into two groups, reparative and epithelial atypias. The latter category was further divided into three subgroups: squamous, columnar, and indeterminate type. The squamous atypia has classical features and is believed to be not significantly related to the IUD. Columnar atypia can strongly suggest cells shed from an adenocarcinoma. Indeterminate type of atypia is characterized by abnormal cells which can resemble cells shed from carcinoma in situ. Unlike the latter, the atypical cells from IUD are usually multinucleated, contain nucleoli, and are not associated with cells from severe cervical atypia. They are probably of endometrial origin.

Adolescent

Rate of cell division in atypias and invasive carcinoma of the uterine cervix of the mouse.

The rate of cell division during a 6-hour period was determined in cervical epithelia from 64 normal mice, 26 mice with cervical atypias, and 8 mice with invasive carcinomas. Cervical atypias and carcinomas were induced by local application of benzo[a]pyrene (BP), and mitosis was arrested with colchicine. Values for the ratio of dividing basal cells to total dividing cells and for the rates of basal cell division for the 6-hour period were both significantly greater in normal epithelia than in atypias, and these values for atypias were greater than those for invasive carcinomas. The differences were not estrous cycle-dependent. There was no evidence that the mechanism of host invasion by squamous tumor cells was due to an increased number of cells in mitoses. The occurrence of areas with mitotic activity suggested the existence of focally distributed and probably alternating, synchronous cell production in normal cervical epithelium. This property was apparently not altered by topical BP application or by carcinogenesis.

Animals

Koilocytotic atypia of the cervix.

Koilocytotic atypia was found in 217 of 858 cervical biopsies obtained during a 26-month period. Koilocytotic change was more common in younger women. Nuclear atypia in the koilocytotic cells was associated with cervical dysplasia in a high proportion of cases. There was a significant difference in the incidence of dysplasia in koilocytosis with marked nuclear atypia when compared to koilocytosis without nuclear atypia. In some cases koilocytosis was associated with vesicular changes in the cervical epithelium. The significance of this change and its association with other abnormalities of the cervix is discussed.

Adolescent

Screening for breast atypias using exfoliative cytology.

A sample of 1744 self-selected, mostly asymptomatic women was used to evaluate exfoliative cytology of nipple secretions as a screening technique for breast atypias. Results indicated: 1) overall frequency of breast fluid recovery was 49%, and related to age, phase of reproductive life, parity, history of lactation and birth control pill use at the time of sampling. 2) Frequency of satisfactory smears was 36% of breast fluid specimens, and related to subject's phase of reproductive life. 3) 2.8% of all satisfactory smears exhibited atypical cells. Biopsy of 4 subjects with atypical smears indicated 3 with nonmalignant epithelial atypias and 1 with early ductal carcinoma. Follow-up of women who did not have atypical smears indicated 12/1092 (1.1%) with nonmalignant epithelial atypias and none with carcinoma. 4) The number of cases of malignant (1) and nonmalignant (7) breast disease detected was close to the expected number in the population sampled (1.98 and 7.25, respectively).

Adult

Fibroadenoma in oral contraceptive users: a histopathologic evaluation of epithelial atypia.

We have reviewed histologically a series of 120 fibroadenomas which formed part of the case material from a previous case-control epidemiological investigation of the relationship between oral contraceptive use and breast disease. We evaluated the epithelial component of the fibroadenoma for degree of cytologic atypia. This study indicates that the reduced risk for fibroadenoma among long-term users of oral contraceptives does not vary according to the degree of epithelial atypia present. This is in contrast to our previously reported findings for fibrocystic disease, in which the decreased frequency of occurrence of the disease in long-term users of oral contraceptives was found only for cases with no minimal epithelial atypia.

Adenofibroma

Atypia in adenomas in three populations with different risk for large bowel cancer: Cali, São Paolo, and New Orleans.

A double-blind study of atypia in colorectal adenomatous polyps was done with autopsy material from Cali, Colombia (low colon risk), São Paulo, Brazil (intermediate risk), and New Orleans, Louisiana (high risk). An interobserver reproducibility of 82% was obtained. The prevalence of atypia in polyps increased with the cancer risk and also with the size of polyps, but some exceptions to the rule were found. The frequency of atypia increased steadily with age in Cali, but it plateaued after age 50 in the higher risk populations.

Aged

The basement membrane in experimentally induced atypias and carcinoma of the uterine cervix in mice. An immunofluorescence study.

Basement membrane-specific antigens of the squamous epithelium of the uterine cervix were investigated in 19 normal mice, in 7 mice with cervical atypia and in 3 mice with invasive carcinoma. Cervical atypia and carcinoma were induced by local application of benzo(a)pyrene. Basement membrane-specific antigens were demonstrated by immunofluorescence with sera from patients with bullous pemphigoid. Both normal squamous cervical epithelium and atypical cervical epithelium showed the presence of a continuous, clearly delineated basement membrane. Clusters of invasive squamous carcinoma were also surrounded by a fluorescent basement membrane which, however, appear fragmented or discontinuous. The results suggest that the ability of cervical squamous cells to secrete basement membrane antigens is not completely lost during carcinogenesis, thus substantiating our previous observations in the cervix of human subjects.

Animals

Fibrocystic breast disease in oral-contraceptive users. A histopathological evaluation of epithelial atypia.

Epidemiological studies show a lower frequency of fibrocystic breast disease among long-term users of oral contraceptives than among women who have never used them. Fibrocystic disease may be a precursor of breast cancer; yet the incidence of breast cancer does not appear to differ between pill-takers and nontakers. To resolve this conflict, we examined the problem from a histologic standpoint in 205 premenopausal women, and found that this decreased frequency applied only to fibrocystic disease in which epithelial atypia was minimal or absent. In women with marked atypia there was no significant difference in frequency among long-term users as compared to women who have never used oral contraceptives. These findings suggest that a spectrum of cystic disease exists and that the long-term use of oral contraceptives protects against the forms of fibrocystic disease that are not firmly associated with an increased risk of breast cancer, but not against the premalignant forms.

Adult

Frequency and significance of epithelial atypia in laryngeal papillomatosis.

The clinical records and microscopic sections from 32 patients were reviewed in an attempt to correlate histopathologic features with clinical behavior. Three general clinical groups were identified on the basis of recurrence rates and extent of papillomatosis. In those lesions with the highest frequency of recurrences, epithelial atypia tended to be most pronounced. Although some of the lesions were quite disturbing, there was no evidence of invasive carcinoma. It remains unknown to date whether these cytologic abnormalities represent a neoplastic alteration or possibly atypia on the basis of rapid, but benign, cellular turnover. Further studies at our center and other institutions are necessary to test the proposed classification which, if validated, would provide a means of predicting the course of the disease and efficacy of the chosen management in these difficult cases.

Adult

Nasal polyposis with stromal atypia. Review of follow-up study of 14 cases.

The clinical, microscopical, and gross pathological features of 14 cases of intranasal and paranasal sinus polyposis with unusual stromal cell atypia are described. In gross appearance, the lesions were polypoid, translucent masses, similar to the usual nasal polyp. Although clinically the lesions were indicative of allergic and inflammatory nasal polyposis, microscopical examination showed numerous large, often pleomorphic histiocytes or facultative fibroblasts that were suggestive or sarcomatous, malignant degeneration. Diagnoses by the original contributing pathologists included embryonal rhabdomyosarcoma, stromal neoplasia, and juvenile masopharyngeal angiofibroma. Follow-up data showed no evidence of neoplasia, despite the remarkable cytological changes found in the stroma. The stromal atypia most likely represents a reactive phenomenon secondary to inflammation.

Adolescent

Genetic Analysis of Early Neoplasia in the Breast: Next-Generation Sequencing of Flat Epithelial Atypia and Associated Ductal and Lobular Lesions.

The molecular features of invasive breast cancers (IBC) have been well-characterized, but less is known about the earlier stages of neoplasia, including oncogenic drivers in early intraductal lesions. Flat epithelial atypia (FEA) is considered the earliest recognized precursor in the low-grade neoplasia pathway, but its mutational repertoire has not been studied, and drivers of the transition to morphologically more advanced lesions are unknown. Herein, we utilized next-generation sequencing to analyze 39 synchronous lesions from 13 patients, including FEA (n = 12) or predominantly FEA with early atypical ductal hyperplasia (FEA/early atypical ductal hyperplasia [ADH], n = 5) and associated ADH (n = 2), ductal carcinoma in situ (ductal carcinoma in situ [DCIS], n = 11), lobular carcinoma in situ (n = 3), and/or IBC with ductal and/or lobular differentiation (n = 6). Aside from 1 DCIS sample, all sequenced lesions in each patient were clonally related to one another. Recurrent alterations in FEA and FEA/early ADH included PIK3CA (69%), NCOR1 (31%), CBFB (31%), RUNX1 (15%), and GATA3 (23%). The mutational repertoire of FEA was similar to The Cancer Genome Atlas luminal IBC, except CBFB and NCOR1 mutations, which were more frequent in FEA and (along with PIK3CA, FOXA1, and CDKN1B) not always identified in paired morphologically advanced lesions. Compared with FEA, DCIS had more mutations and chromosomal copy number changes, including aberrations in PI-3 kinase pathway, transcription factors, chromatin remodeling genes, and TP53. CDH1 mutations identified in lobular carcinoma in situ were absent in paired FEA. Analysis of cases with ductal and lobular heterogeneity, including Rosen's triad, confirmed the shared clonality of the ductal and lobular components with features of genetic divergence. IBC of no special type were genetically similar to DCIS, and tubular carcinomas were similar to FEA. The results reveal the mutational repertoire of FEA and the genetics of early breast neoplasia, highlighting the clonal relationships of FEA to ductal and lobular carcinomas. Luminal breast cancer-associated genetic alterations are present at the earliest morphologically recognized stages of neoplasia.

Humans

Rat mammary gland atypia produced by iodine blockade with perchlorate.

Prior published work from our laboratory concluded that there was a need for appropriate metabolic activity of iodine in breast tissue for normal growth and development. Results from studies in rats that were made iodine deficient showed histological changes in the breasts that were atypical and dysplastic. These tissue findings were further affected by the presence of estrogen and thyroxine. These changes parallel the iodine uptake of the tissues, thus representing a difference in the utilization of iodine by the mammary glands. Using an ion blockade agent, sodium perchlorate, breast tissues lacking iodine were evaluated by both endocrine and histological techniques. A dose-response series was completed that showed that perchlorate therapy for 8 weeks at 400 mg/100 ml produced breast blockade by a reduction in iodine uptake of greater than 52% of the control. At these levels, the histological experimentation showed atypia and some pleomorphism of the cells, particularly in the glands of the lobules. Blockade was less effective in estrogen-treated groups. It is especially notable that both histological changes and uptake reduction were greatest in those breasts that had been rendered euthyroid by thyroxine replacement, thus clearly indicating the necessity of iodine itself for maintenance of normal breast development. By this blockade the responses of iodine inadequacy in the breast were shown to cause abnormal tissue changes relative to the percentage of the block obtained.

Animals

Focal nodular hyperplasia of the liver with alcoholic hyalin bodies and cytologic atypia.

Focal nodular hyperplasia is an uncommon hepatic lesion in which the component hepatocytes are usually histologically normal. A case of focal nodular hyperplasia with cytologically atypical hepatocytes is presented. Light and electron microscopic evidence is given for the presence of alcoholic hyalin in these cells. A review of cytologic changes reported in focal nodular hyperplasia by others is included. To our knowledge, the presence of alcoholic hyalin in focal nodular hyperplasia has not previously been reported.

Aged