scholarly journals New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases

2021 ◽  
Vol 22 (6) ◽  
pp. 2831
Author(s):  
Ryan Bensen ◽  
John Brognard
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Fate ◽  
Squamous Cell ◽  
Copy Number Gain ◽  
Genetic Alterations ◽  
Distal Portion ◽  
Squamous Cell Carcinomas ◽  
Cell Fate Decisions ◽  
Genetic Landscape

Squamous cell carcinomas of the lung, head and neck, esophagus, and cervix account for more than two million cases of cancer per year worldwide with very few targetable therapies available and minimal clinical improvement in the past three decades. Although these carcinomas are differentiated anatomically, their genetic landscape shares numerous common genetic alterations. Amplification of the third chromosome’s distal portion (3q) is a distinguishing genetic alteration in most of these carcinomas and leads to copy-number gain and amplification of numerous oncogenic proteins. This area of the chromosome harbors known oncogenes involved in squamous cell fate decisions and differentiation, including TP63, SOX2, ECT2, and PIK3CA. Furthermore, novel targetable oncogenic kinases within this amplicon include PRKCI, PAK2, MAP3K13, and TNIK. TCGA analysis of these genes identified amplification in more than 20% of clinical squamous cell carcinoma samples, correlating with a significant decrease in overall patient survival. Alteration of these genes frequently co-occurs and is dependent on 3q-chromosome amplification. The dependency of cancer cells on these amplified kinases provides a route toward personalized medicine in squamous cell carcinoma patients through development of small-molecules targeting these kinases.

Squamous Cell Carcinoma Variants of the Upper Aerodigestive Tract: A Comprehensive Review With a Focus on Genetic Alterations

2014 ◽  
Vol 138 (6) ◽  
pp. 731-744 ◽  
Author(s):  
Akeesha A. Shah ◽  
Susanne K. Jeffus ◽  
Edward B. Stelow
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nuclear Protein ◽  
Genetic Alterations ◽  
Squamous Cell Carcinomas ◽  
Aerodigestive Tract ◽  
Treatment Modalities ◽  
Upper Aerodigestive Tract ◽  
Molecular Alterations

Context.— Squamous cell carcinoma of the upper aerodigestive tract is a heterogenous entity. Although conventional squamous cell carcinomas are easily recognized, the morphologic variants of squamous cell carcinoma can present a diagnostic challenge. Familiarity with these variants is necessary because many are associated with unique risk factors and are characterized by specific molecular alterations (eg, nuclear protein in testis midline carcinomas). Perhaps the most important distinction is in identifying viral-related from nonviral-related carcinomas. The accurate diagnosis of these variants is necessary for prognostic and therapeutic reasons. Objectives.— To provide a clinicopathologic overview and summary of the molecular alterations of the common squamous cell carcinoma variants, including verrucous, spindle cell, acantholytic, adenosquamous, basaloid, and papillary squamous cell carcinoma, as well as nuclear protein in testis midline carcinoma, and to discuss the distinguishing features of human papillomavirus- and Epstein-Barr virus-related squamous cell carcinomas. Data Sources.— Published peer-reviewed literature. Conclusions.— Familiarity with squamous cell carcinoma variants is essential for proper diagnosis and to guide appropriate clinical management. Further insight into the molecular alterations underlying those variants may lead to alterations in existing treatment approaches and to evolution of novel treatment modalities.

scholarly journals Whole exome sequencing and deep sequencing of esophageal squamous cell carcinoma and adenocarcinoma in Japanese patients using the Japanese version of the Genome Atlas, JCGA

Esophagus ◽  
2021 ◽  
Author(s):  
Eisuke Booka ◽  
Yasuhiro Tsubosa ◽  
Tomoya Yokota ◽  
Shuhei Mayanagi ◽  
Kenjiro Ishii ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Somatic Mutations ◽  
Molecular Targets ◽  
Japanese Version ◽  
Japanese Patients ◽  
Genetic Alterations ◽  
Genome Atlas

Abstract Background Recent comprehensive mutation analyses have revealed a relatively small number of driver mutations in esophageal cancer, implicating a limited number of molecular targets, most of which are also implicated in squamous cell carcinoma. Methods In this study, we investigated genetic alterations in 44 esophageal squamous cell carcinomas (ESCC) and 8 adenocarcinomas (EAC) from Japanese patients as potential molecular targets, based on data from the Japanese version of The Genome Atlas (JCGA). Results Esophageal cancer was characterized by TP53 somatic mutations in ESCC (39/44, 88.6%) and EAC (5/8, 62.5%). In addition to TP53 mutations, somatic mutations in NFE2L2 (16/44, 36.4%), CDKN2A (7/44, 15.9%), and KMT2D (7/44, 15.9%) were more frequently detected in ESCC than in EAC. WRN-truncated type mutations that lead to genomic instability correlate with EAC, but not ESCC. ESCC samples were enriched in ALDH2-associated mutational signature 16 as well as the APOBEC signature. Patients with FAT2 mutations had significantly poorer overall survival compared with those with wild-type status at FAT2 (p < 0.05). Patients with EP300 or PTPRD mutations also had poor progression-free survival compared with respective wild-types (p < 0.05 or p < 0.001). Conclusions These findings may facilitate future precision medicine approaches based on genomic profiling in ESCC and EAC.

scholarly journals Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucía Trilla-Fuertes ◽  
Angelo Gámez-Pozo ◽  
Joan Maurel ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Anal Carcinoma ◽  
Genetic Alterations ◽  
Daily Clinical Practice ◽  
Complete Regression ◽  
Anal Squamous Cell Carcinoma

AbstractSquamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.

scholarly journals Clinicopathological Risk Factors for Contralateral Lymph Node Metastases in Intraoral Squamous Cell Carcinoma: A Study of 331 Cases

2021 ◽  
Vol 28 (3) ◽  
pp. 1886-1898
Author(s):  
Christian Flörke ◽  
Aydin Gülses ◽  
Christina-Randi Altmann ◽  
Jörg Wiltfang ◽  
Henning Wieker ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymph Node Metastases ◽  
Squamous Cell Carcinomas ◽  
Patient Specific ◽  
Infiltration Depth ◽  
Tumor Grading ◽  
Node Metastases

The current study aimed to examine the effects of clinicopathological factors, including the region, midline involvement, T classification, histological grade, and differentiation of the tumor on the rate of contralateral lymph node metastasis for oral squamous cell carcinoma and to assess their effects on survival rates. A total of 331 patients with intraoral squamous cell carcinomas were included. The influence of tumor location, T status, midline involvement, tumor grading, and the infiltration depth of the tumor on the pattern of metastasis was evaluated. Additionally, the effect of contralateral metastases on the prognosis was examined. Metastases of the contralateral side occurred most frequently in squamous cell carcinomas of the palate and floor of the mouth. Furthermore, tumors with a high T status resulted in significantly higher rates of contralateral metastases. Similarly, the midline involvement, tumor grading, existing ipsilateral metastases, and the infiltration depth of the tumor had a highly significant influence on the development of lymph node metastases on the opposite side. Oral squamous cell carcinomas require a patient-specific decision. There is an ongoing need for further prospective studies to confirm the validity of the prognostic factors described herein.

Invasive Squamous Cell Carcinoma with Osteomyelitis of the Foot

2015 ◽  
Vol 105 (4) ◽  
pp. 374-376
Author(s):  
Morteza Khaladj ◽  
Rose-Mary Mbibong ◽  
Nisha Shah ◽  
Ayesha Mohiuddin ◽  
Aqsa Siddiqui
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Chronic Wounds ◽  
Squamous Cell Carcinomas ◽  
Initial Presentation ◽  
Invasive Squamous Cell Carcinoma ◽  
The Sun ◽  
The Third

Squamous cell carcinomas are often seen on the sun-exposed areas of the skin and are rarely observed on the digits of the foot. However, there have been incidences of squamous cell carcinoma developing in the presence of chronic wounds with osteomyelitis, thus complicating the treatment. We present a patient with osteomyelitis who developed invasive squamous cell carcinoma of the third digit. We conclude that wounds with osteomyelitis may have underlying pathologic abnormalities that are not obvious on initial presentation.

Granulocytosis, a Paraneoplastic Syndrome Associated With Non-Glandular Squamous Cell Carcinomas (NGSCC) in the Tg.rasH2 Studies

2021 ◽  
pp. 019262332110557
Author(s):  
Madhav Paranjpe ◽  
Peter Mann ◽  
Melissa Denton
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Paraneoplastic Syndrome ◽  
Statistical Significance ◽  
Squamous Cell Carcinomas ◽  
Rare Tumor ◽  
Male Mice ◽  
Control Male ◽  
Control Female

Non-glandular squamous cell carcinoma (NGSCC) is an extremely rare tumor in Tg.raH2 mice. There have been 5 NGSCC in 1615 control male mice (0.31%) and 2 NGSCC in 1560 control female mice (0.13%) on 26-week carcinogenicity studies, with a range of 0 to 1 of per group per sex in each study without statistical significance in 52 male and 51 female studies conducted in Tg.rasH2 mice. Every case of NGSCC was accompanied by profound granulocytosis.

p16 Expression in Keratoacanthomas and Squamous Cell Carcinomas of the Skin: An Immunohistochemical Study

2006 ◽  
Vol 130 (1) ◽  
pp. 69-73
Author(s):  
Emad Kaabipour ◽  
Helen M. Haupt ◽  
Jere B. Stern ◽  
Peter A. Kanetsky ◽  
Victoria F. Podolski ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immunohistochemical Study ◽  
Squamous Cell Carcinomas ◽  
Diagnostic Dilemma ◽  
Significant Difference ◽  
P16 Expression

Abstract Context.—Distinguishing between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is not an uncommon histologic diagnostic dilemma. Objective.—To determine if p16 expression is useful in the differential diagnosis of SCC and KA. Design.—We studied the expression of p16 by immunohistochemistry in 24 KAs, 24 infiltrating SCCs of the skin, 4 histologically indeterminate lesions, and 8 nonmalignant keratoses. Results.—A range of immunohistochemical p16 expression was seen in KAs and SCCs in terms of the thickness of lesional staining and the percentage of cells staining. No significant difference in measures of p16 expression was identified among the KAs, the SCCs, the indeterminate lesions, or the benign keratoses. Conclusions.—These findings suggest that p16 is not a useful marker to distinguish between KA and SCC, supporting the similarity between the 2 lesions; p16 alterations appear to play a role in the pathogenesis of both KA and SCC.

Sign in / Sign up

Export Citation Format

Share Document