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.
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.
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.
Gene profiling using a customized NanoString platform can be applied to routine mycosis fungoides (MF) samples, revealing their specific molecular features. This study shows that MF samples carry a ...signature derived from individual molecular features found in consecutive biopsies.
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.
Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature.
The main goal of ...this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome.
This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology.
The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature.
The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome.
The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.
Superficial acral fibromyxoma (SAF) is a benign, soft tissue neoplasm preferably located on the digits.
We collected 13 cases of SAF and evaluated their clinical, histopathologic, and ...immunohistochemical features.
This study included 9 males and 4 females, median age 54 years. The patients presented with a solitary asymptomatic or tender mass, most of them arising on fingers or toes. Histopathologically all lesions consisted of nonencapsulated dermal nodules, composed of spindled cells with variable myxoid and/or fibrotic stroma. Some lesions were well circumscribed (6/12, 50%), whereas other ones appeared poorly demarcated (6/12, 50%). The stroma was predominantly myxoid (53%), myxoid-collagenous (31%) or mostly collagenous (15%). Neoplastic cells expressed immunoreactivity for CD34 (8/11), CD99 (9/12), and nestin (7/7); whereas MUC4 (0/11) and Bcl-2 (0/7) resulted negative.
Nestin is the best immunohistochemical marker for SAF with higher sensitivity than CD34, although nestin is also positive in dermatofibrosarcoma protuberans and therefore is not helpful in differential diagnosis between SAF and dermatofibrosarcoma protuberans. Cellular digital fibromas and acquired reactive digital fibroma probably are neoplasms closely related to SAF. The homogeneous reactivity for CD99, the negativity for Bcl-2 and lack of the honeycomb infiltration of the subcutis help to rule out myxoid dermatofibrosarcoma protuberans, whereas the negativity for MUC4 and Bcl-2 are helpful tools to rule out low-grade fibromyxoid sarcoma and spindled-cell lipoma, respectively.
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