TERT promoter mutation in sebaceous neoplasms Muñoz-Jiménez, María-Teresa; Blanco, Leyla; Ruano, Yolanda ...
Virchows Archiv : an international journal of pathology,
09/2021, Letnik:
479, Številka:
3
Journal Article
Recenzirano
TERT
promoter (
TERT
p) mutations widely occur in multiple human neoplasms, and they have been related to different clinicopathological features. To date, this mutation has not been identified in ...sebaceous tumors. Here, we analyzed
TERT
p mutations in 91 sebaceous neoplasms (17 adenomas, 45 sebaceomas, and 29 carcinomas). We detected mutations in 26.7% (8 of 29) of sebaceous carcinomas by pyrosequencing and Sanger sequencing. No mutation was detected in adenomas or sebaceomas. The difference was significant between sebaceoma and carcinoma. The most frequent
TERT
p mutations were C228T and C250T in 37.5% (3 of 8) of mutated cases each one. The mutation was not associated with poor clinical evolution. Using NGS, 20 of 29 (68.5%) sebaceous carcinomas harbored mutations in 8 of the 30 genes analyzed (TP53,
TERT
p, EGFR, ATRX, PDGFRA, CDKN2A, PTEN, and ACVR1). With immunohistochemistry, only 1 of 8 (12.5%)
TERT
p-mutated carcinomas lacked mismatch repair (MMR) protein expression compared to 6 of 21 (31.6%) of non-mutated ones. Sebaceous carcinomas with MMR protein expression had significantly higher frequency of total mutations and TP53 and
TERT
p mutations than MMR protein-deficient carcinomas. In conclusion,
TERT
p mutation has been detected in sebaceous carcinomas, and its presence could be useful to differentiate sebaceous carcinoma from sebaceoma, a difficult histopathological challenge.
The characterization of molecular alterations of primary breast carcinomas (BC) and their cutaneous metastases (CM) to identify genes involved in the metastatic process have not yet been completely ...accomplished.
To investigate the molecular alterations of BC and their CM, a total of 66 samples (33 BC and 33 CM) from 33 patients were analyzed by immunohistochemical and massive parallel sequencing analyses. In addition, the clinicopathological characteristics of patients and tumors were analyzed.
Triple negative (TN) BCs were overrepresented (36.4%) among tumors that developed CM. A change of tumor surrogate molecular type in metastases was found in 15% of patients and 48.5% of the CM presented some additional molecular alteration with respect to the primary tumor, the most frequent were amplification of
and
, and mutations in
and
. Survival was related to histological grade, tumor surrogate molecular type and
mutations in the univariate analysis but only the tumor surrogate molecular type remained as a prognostic factor in the multivariate analysis.
The TN molecular type has a greater risk of developing skin metastases. There are phenotypic changes and additional molecular alterations in skin metastases compared to the corresponding primary breast tumors in nearly half of the patients. Although these changes do not follow a specific pattern and varied from patient to patient, they could impact on the treatment. More studies with larger patient and sample cohorts are needed.
Background:
Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety ...and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment.
Methods:
Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array.
Results:
Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6–41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15–3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response.
Conclusion:
Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data.
Trial registration:
EudraCT 2009-018171-13
The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the ...prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2−) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2− early breast cancer.
Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical ...presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
To study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.
Tumour tissue samples ...from 148 patients with advanced GC were studied for HER2 by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and dual colour silver enhanced in situ hybridisation (dc-SISH) methods. Clinicopathological data from all patients were collected. Progression free survival and overall survival were also analysed.
Mean age was 67 (33-83) years; 75% were male subjects, and 51% had intestinal histological type. HER2+ rates were 10.1% (15/148) by IHC, 18.2% (27/148) by FISH+ or 21.6% (32/148) by dc-SISH+. There were significant differences in HER2+ rates according to histological type when FISH (intestinal, 23%; no intestinal, 4%; p<0.0001) or dc-SISH (intestinal, 26%; no intestinal, 6%; p<0.0001) amplification techniques were used. Median overall survival was significantly longer in HER2+ patients despite the determination technique used: IHC (21.4 vs 9.8 months, HR 0.42; p=0.005); FISH (19.6 vs 9.7 months, HR 0.49; p=0.007) or dc-SISH (19.6 vs 9.7 months, HR 0.53; p=0.009). Factors associated with favourable survival in the multivariate analysis were intestinal type and Her2+ determination by IHC, FISH or dc-SISH.
HER2 gene amplification is significantly associated with patient survival. HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2+ GC patients who are candidates to be treated with anti-HER2 therapies.
Background Cribriform carcinoma is the histopathologic variant of cutaneous apocrine carcinoma characterized by interconnected solid aggregations of neoplastic cells that are punctuated by small ...round spaces. Objective To describe the histopathologic and immunohistochemical characteristics of this under-recognized cutaneous adnexal neoplasm. Methods Twenty-six cases of primary cutaneous cribriform apocrine carcinoma were clinically, histopathologically, and immunohistochemically studied. Results Seven neoplasms arose in males and 19 in females. The median age of the patients was 47.8 years. The lower and upper limbs were the most frequent sites. Histopathologically, the neoplasms consisted of well-circumscribed dermal nodules composed of multiple, interconnected, solid aggregations of basophilic epithelial cells that were punctuated by small round spaces. Immunohistochemically, the neoplastic cells expressed immunoreactivity for MNF116, AE1/AE3, Cam 5.2, cytokeratin 7, carcinoembryonic antigen, and epithelial membrane antigen. Limitations All specimens came from dermatopathology laboratories, and some inherent selection bias may exist. Conclusions Primary cutaneous cribriform apocrine carcinoma is a distinctive but little-known variant of cutaneous apocrine carcinoma.
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