Variant Of Squamous Cell Carcinoma Research Articles

Clear cell squamous cell carcinoma of the tongue exhibits characteristics as an undifferentiated squamous cell carcinoma

Clear cell squamous cell carcinoma (CCSCC), where cells show abundant clear cytoplasm, –is a variant of squamous cell carcinoma (SCC) and a rare entity in the oral cavity. The characteristics of CCSCC, especially in immunohistochemical features, remain unclear. We characterized a case of CCSCC arising from the oral mucosal epithelium of tongue, where the clear cell lesion accounted for a predominant portion of the tumor. This CCSCC, which was partially surrounded by conventional SCC, exhibited cellular atypia immunohistopathologically and histopathologically with a high Ki-67 index, increased number of mitotic figures and enlarged nuclei. Intravascular invasion of the carcinoma cells was also observed. Furthermore, the CCSCC recurred and metastasized to the cervical lymph nodes and both lungs three months after resection. Immunohistochemical analyses demonstrated decreased expression of p40 (an isoform of SCC marker p63), ADP-ribosylation factor (ARF)-like 4c (ARL4C), yes-associated protein (YAP) and 5-methylcytosine (5mC) in the CCSCC lesion compared with the surrounding SCC lesion, where the expression of ARL4C was upregulated compared with non-tumor region and YAP showed nuclear translocation. In addition, siRNA loss-of-function experiments revealed that p63 expression was required for ARL4C expression and DNA methylation was induced by p63 and YAP/transcriptional co-activator with PDZ-binding motif (TAZ) signaling in oral SCC cell lines. These results suggest that CCSCC, in which several markers of SCC-associated intracellular signaling pathways are downregulated, together with evidence of altered epigenetic regulation, is characterized as an undifferentiated SCC variant.

Epithelial-Mesenchymal Transition Marker Brachyury Is Not Expressed in Spindle Cell Carcinoma of the Head & Neck

Introduction. Epithelial-mesenchymal transition (EMT) is a complex biologic process by which epithelial cells lose their cytomorphologic characteristics and assume the phenotype of mesenchymal cells. EMT is essential to normal human embryogenesis, and also occurs in wound healing, tissue repair and cancer progression. Acquisition of a mesenchymal phenotype via EMT enhances the migratory capacity of carcinoma cells, increasing their metastatic capability and worsening prognosis for patients. One emerging marker of EMT is brachyury, a T-box transcription factor protein. Recent studies have demonstrated upregulation of brachyury in several carcinoma types, includ- ing squamous cell carcinoma (SCC). Spindle cell carcinoma (SpCC) is a variant of SCC in which cancer cells have a predominantly spindled phenotype. Whether brachyury is expressed in SpCC and contributes to this pheno- typic change is not clear. Objective.To examine brachyury expression by immunohistochemistry in SpCC of the head & neck, hypothesizing that brachyury expression is increased in SpCC, as compared with other forms of SCC. Methods.Immunohistochemical staining for brachyury was performed on 20 head and neck carcinoma cases per group in each of four groups: SpCC; moderately- to well-differentiated SCC; moderately- to poorly-differentiated SCC; and verrucous carcinoma (VC). Uninflamed fibroma was the negative control; and human chordoma, along with a 14.5-day-old mouse embryo, were positive controls. Evaluation of brachyury reactivity was completed by light microscopy. Results.Brachyury expression was not seen in any of the experimental groups. Nuclear reactiv- ity was present in both positive controls, including within chordoma cells, and within the nucleus pulposus of the mouse embryo. Conclusions.Brachyury does not appear to be involved in the cytomorphologic changes present in SpCC, nor is it expressed in any head & neck SCC variants. Our results are contrary to those found in previous reports. This result supports the hypothesis that an alternate mechanism contributes to the phenotype of SpCC.

Outcomes of Patients With Adenosquamous Carcinoma of the Head and Neck after Definitive Treatment

<h3>Purpose/Objective(s)</h3> Adenosquamous carcinoma of the head and neck (ASC-HN) is a rare and aggressive variant of squamous cell carcinoma (SCC). Limited data suggests inferior outcomes compared to conventional SCC. We report one of the largest single institutional experiences of this disease in patients treated definitively to further elucidate oncologic outcomes. <h3>Materials/Methods</h3> Patients with non-metastatic ASC-HN treated definitively between 2003 and 2021 were identified retrospectively from an IRB approved database with histology verified by head and neck pathologists. All tumors of the oropharynx were tested for p16 and/or HPV to document HPV associated disease. For non-oropharyngeal lesions, a designation of HPV positivity required the presence of HPV DNA/RNA per FISH. Actuarial analyses were performed for PFS and OS. <h3>Results</h3> 29 patients with ASC-HN (72.4% male, 93.1% Caucasian) with median age of 66 (range 34-91) and a median follow up of 33 months (range 6.6-126.7) were identified. The most common primary tumor sites were: oropharynx (27.6%), oral cavity (20.7%), nasal cavity (17.2%), and larynx (17.2%). 3 patients had primaries in the hypopharynx, nasopharynx and parotid gland respectively. 11 patients (37.9%) were HPV positive of whom 8 had oropharyngeal primaries. The majority (n=23, 79.3%) were treated with primary surgery of whom 19 (82.6%) received adjuvant radiation (RT) to a median dose of 60 Gy (range 36-70 Gy) with 7 receiving concurrent chemotherapy. 6 patients were treated with definitive RT to a median dose of 70 Gy with two receiving concurrent chemotherapy. There were 10 recurrences (34.5%) which occurred at a median of 14.3 months (range 5.4-28) after diagnosis including 8 loco-regional and 2 distant recurrences. Recurrences were documented in patients with primary salivary gland, oral cavity, laryngeal, hypo-pharyngeal, and oropharyngeal tumors. 3 of the 10 recurrences were in patients with HPV positive disease. Among the 6 patients treated with definitive radiation or chemo-radiation no failures were observed. 9 patients (31%) were deceased at the time of analysis. Overall 3 year PFS and OS were 54.2% and 72.9% respectively. 3 year PFS and OS were 45.6% and 69.6% for primary surgery and 83.3% and 83.3% in the definitive RT group. 3 year PFS was 50% and 75% for HPV negative and positive patients respectively. <h3>Conclusion</h3> In our single institutional experience of 29 patients with adenosquamous carcinoma of the head and neck there was a 34.5% recurrence rate. Loco-regional recurrence was the primary mode of failure.

Ocular surface squamous neoplasia with orbital tumour extension: risk factors and outcomes.

To describe the risk factors, clinical features, histopathology, treatment, and outcomes of patients with orbital tumour extension of ocular surface squamous neoplasia (OSSN). Retrospective study of 51 patients with orbital tumour extension (cases) and 360 patients without orbital extension (controls). Of 1,653 patients with OSSN, orbital tumour extension was noted in 51 (3%) cases. The risk factors for orbital tumour extension included outdoor occupation (p < 0.03; Odds ratio (OR) = 1.96), Human Immunodeficiency Virus (HIV) infection (p < 0.0001; OR = 5.81), prolonged duration of symptoms (p = 0.01; OR = 1.02), tumour bilaterality (p = 0.02; OR = 2.92), forniceal and tarsal conjunctival involvement, diffuse tumour (p < 0.0001; OR = 9.13), inferior quadrantic location (p < 0.0001; OR = 7.51), increased tumour thickness (p = 0.04; OR = 1.59), higher % of ocular surface involvement (p = 0.002; OR = 1.12), nodular (p = 0.002; OR = 2.61) and nodulo-ulcerative (p < 0.0001; OR = 11.05) tumour morphology, poorly differentiated tumours (p = 0.006; OR = 4.23); invasive squamous cell carcinoma (SCC) (p < 0.0001; OR = 29.76), spindle cell and mucoepidermoid variant (p = 0.02; OR = 16.94) tumours. At a mean follow-up period of 27 months, tumour recurrence in the socket was noted in 1 (2%), locoregional lymph node metastasis (LNM) in 15 (29%) patients, and nine (18%) patients died due to systemic metastasis (SM). T4 tumour at presentation was a risk factor for LNM (p = 0.01; Hazard ratio (HR) = 5.60) and SM (p = 0.0003; HR = 5.09). Orbital extension of OSSN is rare. Outdoor occupation, HIV infection, larger and thicker tumours in the inferior quadrant with forniceal and/or tarsal conjunctival involvement with nodular or noduloulcerative morphology, poor tumour differentiation, SCC, spindle cell and mucoepidermoid variants on histopathology are at increased risk for orbital tumour extension.

Persistent perianal “warts”

Persistent perianal “warts”

Incidence of histopathological variants of oral squamous cell carcinoma: An institutional study

Squamous cell carcinoma is the most important and the most common malignant mucosal neoplasm of the head and neck accounting for over 90% of all malignancies. Conventional oral Squamous cell carcinoma is frequently present in general cancerous conditions. It is bundled up with six different variants. Histomorphologically every variant shows a unique appearance. This raises an opportunity for the different diagnostic consideration with the precise management decision.All cases of OSCC reported at our institution Dentopath Pathologies Amravati in past two months were scrutinized. Representative sections containing the full thickness of the tumor were used for histopathological grading. The structure and identification of carcinomas were done microscopically by two expert dentopathologist.In the present study, we screened 100 slides of a conventional epithelial cell carcinoma. Amonst which 30 Slides showed the verrucous carcinoma. On 5 slides adenoid squamous cell carcinoma were observed. Incidence of Papillary squamous cell carcinoma and basaloid squamous cell carcinoma was only 1 out of 100 slides each. Whereas, the spindle cell/sarcomatoid carcinoma was observed on 2 slides. Adenosquamous carcinoma is the rarest variant and hence no incidence of this carcinoma were observed in our study. The behavior of the OSCC varies amongst due to the presence of different morphological type of tumor. A few studies on OSCC malignancy grading with different clinical parameters were made. In the present study different types of variants are seen according to their histopathological appearances.Histopathological knowledge is very important for the precise diagnosis. Squamous cell carcinoma is the most common neoplasm of oral cavity. However, variants of the same show very less frequency. Hence, it became challenge for the appropriate diagnosis as many times a misdiagnosis affects the course of treatment of the patient

Clinical, histopathological and immunohistochemical study of keratoacanthoma.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

Intravesical Therapy for Non-Muscle-Invasive Bladder Cancer: What Is the Real Impact of Squamous Cell Carcinoma Variant on Oncological Outcomes?

Background and Objectives: To evaluate the oncological impact of squamous cell carcinoma (SCC) variant in patients submitted to intravesical therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: Between January 2015 and January 2020, patients with conventional urothelial NMIBC (TCC) or urothelial NMIBC with SCC variant (TCC + SCC) and submitted to adjuvant intravesical therapies were collected. Kaplan–Meier analyses targeted disease recurrence and progression. Uni- and multivariable Cox regression analyses were used to test the role of SCC on disease recurrence and/or progression. Results: A total of 32 patients out of 353 had SCC at diagnosis. Recurrence was observed in 42% of TCC and 44% of TCC + SCC patients (p = 0.88), while progression was observed in 12% of both TCC and TCC + SCC patients (p = 0.78). At multivariable Cox regression analyses, the presence of SCC variant was not associated with higher rates of neither recurrence (p = 0.663) nor progression (p = 0.582). Conclusions: We presented data from the largest series on patients with TCC and concomitant SCC histological variant managed with intravesical therapy (BCG or MMC). No significant differences were found in term of recurrence and progression between TCC and TCC + SCC. Despite the limited sample size, this study paves the way for a possible implementation of the use of intravesical BCG and MMC in NMIBC with histological variants.

Spindle Cell Squamous Cell Carcinoma of the Tongue: A Rare Variant at an Even Rarer Location

Spindle cell carcinoma (SpCC) is an unusual variant of squamous cell carcinoma (S.C.C.) of the head and neck region. It is a rare biphasic neoplasm.&nbsp; SpCC is an unusual morphological variant of S.C.C.&nbsp; It is characterized by the presence of both carcinomatous as well as sarcomatous component and accounts for 2 to 3% of all the S.C.C.s. Seven years ago, the W.H.O. classification has placed this tumor under the malignant epithelial tumors and called it SpCC. The histogenesis of spindle c

Primary basaloid squamous cell carcinoma of the parotid gland mimicking metastasis of basal cell carcinoma of the contralateral periorbital region: case report

Basaloid squamous cell carcinoma (BSCC) in the head and neck area is extremely rare. World Health Organization defined BSCC as a high-grade variant of squamous cell carcinoma composed both of basaloid and squamous components. Due to its histologic similarity to other parotid gland malignancies it can be easily misdiagnosed. We report first case of BSCC arising from parotid gland in Europe and second in the world literature. A 72-year-old female patient was referred to the Department of Cranio-Maxillofacial Surgery of the Jagiellonian University in Poland due to the tumor arising from the right parotid gland. Patient had history of multiple excisions of recurrent basal cell carcinoma (BCC) of the left periorbital region. We performed total parotidectomy with facial nerve preservation. Postoperative radiotherapy (PORT) was carried out, and the patient received 70 Gy in 30 fractions on the parotid gland area due to the fact that the tumor adhered to the facial nerve trunk and branches, additionally 60 Gy on the neck area in I, II and III levels. To distinguish the tumor of the parotid gland from the possible metastasis from BCC of the left medial canthal region previous histopathological slides were also reexamined and compared with histopathological examination of removed parotid gland tumor. Histological examination confirmed a rare case of BSCC arising from the parotid gland. 14 months of the follow up did not show local recurrence or distant metastasis.

Nasal septal verrucous carcinoma presenting as a cutaneous horn

Background: Cutaneous horn arising from the nasal vestibule is an extremely rare entity with only four published case reports to date. Although cutaneous horns are commonly benign, the risk of it harboring a malignant or pre-malignant process is about one in three. Verrucous carcinoma is a variant of squamous cell carcinoma (SCC) that typically presents in the oral cavity, and very rarely in the nasal cavity. Case Presentation: We report a 78-year-old female who presented with a rapidly enlarging right naris cutaneous horn of 5 months duration. Computed tomography scan showed a heterogeneously enhancing mass at the right anterior nasal cavity with no overt bone or cartilage destruction. Differential diagnoses included seborrheic keratosis, actinic keratosis, viral wart, and malignant tumors such as SCC. She underwent an excision biopsy and histology confirmed the diagnosis of a pT1 verrucous SCC. Conclusion: Due to the rarity of the site of the disease, management of sinonasal verrucous carcinoma is generally derived from management options of other subsites in the head and neck region. The preferred treatment modality is surgical excision, while primary radiotherapy is an emerging treatment alternative in poor surgical candidates.

Primary Cutaneous Adenosquamous Carcinoma of Scalp: A Rare Variant

Adenosquamous carcinoma is an aggressive and rare variant of squamous cell carcinoma that has both squamous and glandular differentiation. We present a case of occipital scalp adenosquamous carcinoma in a 43-year-old male who presented with occipital mass that was initially marble in size, which progressively enlarges over years. There were no constitutional symptoms. No neurological deficit and locoregional lymph nodes were not palpable. Contrast enhanced computerized tomography brain revealed a non-enhancing midline occipital scalp mass with no intracranial extension or bony involvement. Tissue biopsy of the occipital mass was performed, and preliminary microscopic and immunohistochemistry studies suggested adenosquamous carcinoma. The tumor was completely excised with wide local excision, followed by skull burring and primary closure.

Prognostic Role of Histological Scoring of Oral Squamous Cell Carcinoma

Introduction: Diagnosis of oral squamous cell carcinomas require assessment of parameters like histologic grade, tumour depth of invasion, lymphovascular invasion, perineural invasion, margin status, worst pattern of Invasion, But for treatment purpose only Tumour, Nodes and Metastases (TNM) staging is given importance. Aim: To develop a scoring system based on different histopathological tumour characteristics and to know its prognostic role in oral squamous cell carcinomas. Materials and Methods: This retrospective study was conducted in Department of Pathology at Great Eastern Medical School and Hospital, Srikakulam, Andhra Pradesh, India, from September 2011 to August 2016 and data was followed-up for 5 years, upto August 2021. Resection of primary oral lesions with cervical lymph nodal dissection were included in the study, while cases of non squamous cell carcinomas, variants of squamous cell carcinoma, post radiotherapy cases, defaulted cases, patients who lost for follow-up were excluded. The Histoscore (H score) was obtained by the scores of all histopathological tumour characteristics and it ranged from 2 to 11.This H score was divided into three groups and mean survival period of these three Histoscore Groups (HS groups) were calculated for their prognostic use (Group 1 has score 2 to 5, Group 2 has score 6 to 8, Group 3 has score 9 to 11). Medians and ranges were used to summarize continuous data, while frequency counts and percentages were used for categorical data. Kaplan-Meier’s analysis was used for evaluating 5 years survival. The p-value &lt;0.05 was considered as statistically significant. Results: A total of 90 cases were studied. Mean survival period was compared to HS groups, Group 1 had 64±7.59 months, Group 2 had 40.8±11.88 months, Group 3 had 26.06±12.25 months with a p-value &lt;0.001, indicating it as a statistically significant parameter. Based on TNM staging, majority were in T2 (N=41,45.55%), N1(N=34,37.77%) and Mx (N=87,96.66%). Conclusion: Histoscore groups of the oral squamous cell carcinomas have significant differences in the mean survival period among themselves. Hence, this histoscore groups can be an additive to the TNM classification, which provide more prognostic information to the oncologists.

KDM6A missense variants hamper H3 histone demethylation in lung squamous cell carcinoma

KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it is also a known cancer driver gene, with multiple somatic mutations found in a few cancer types. In this study, we looked at eleven missense variants in lung squamous cell carcinoma, one of the most common lung cancer subtypes, to see how they affect the KDM6A catalytic mechanisms. We found that they influence the interaction with histone H3 and the exposure of the trimethylated Lys27, which is critical for wild-type physiological function to varying degrees, by altering the conformational transition.

Extraorally proliferating verrucous carcinoma of buccal mucosa mimicking squamous cell carcinoma: A rare case presentation

Verrucous carcinoma (VC) (Ackerman's tumor/Snuff dipper's cancer) is a variant of oral squamous cell carcinoma (SCC) with minimum aggressive potential. The most common sites of involvement in the head-and-neck regions are oral cavity and larynx. VC of the oral cavity is a different clinicopathologic tumor distinguished from the usual SCC because of its local invasiveness, nonmetastasizing behavior, and special clinical appearance, but long-standing cases have shown transformation into SCC. An accurate pathological diagnosis is difficult because of an inadequate tumor sample for the study, and more importantly, a close collaboration is needed between a clinician and a pathologist to achieve the correct diagnosis. In this article, we discuss a case of 42-year-old male with VC of the left buccal mucosa which was proliferating extraorally.

Les carcinomes du pénis : une revue des différents types histologiques

The most frequent cancer of the penis is the squamous cell carcinoma. Several variants of squamous cell carcinoma exist. It is important to make a difference between squamous cell carcinomas with and without a HPV infection. Furthermore, it is extremely important to recognize the different variants as their prognosis differs. These tumors are rare therefore classifying them can be challenging. This review is supposed to give an overview on the existing entities since 2016, but also allows a glimpse into the future with some comments on the upcoming WHO classification 2021.

Association of HPV and EBV in Oral Verrucous Squamous Cell Carcinoma and Oral Verrucous Hyperplasia

Objective Oral verrucous squamous cell carcinoma or oral verrucous carcinoma (OVC) is a rare verrucous variant of oral squamous cell carcinoma (OSCC), which accounts for 2 to 12% of all oral carcinomas. Oral verrucous hyperplasia (OVH) is clinically similar to OVC and has been proposed to be a precursor lesion of OVC. Etiopathogenesis of both lesions is still inconspicuous. Oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV) have been reported to be associated with some cases of OSCC, and we hypothesized that it may act as a causative agent of these verrucous lesions. This study aimed to investigate frequency of HPV and EBV infections in OVC and OVH. Material and Methods Using polymerase chain reaction (PCR), a total of 35 formalin-fixed paraffin-embedded (FFPE) tissue samples, including 27 OVC samples and 8 OVH samples, were investigated for HPV and EBV infection. HeLa and B95-8 cell lines were used as positive controls of HPV and EBV PCR, respectively. Results All OVC and OVH samples show a positivity to GAPDH , whereas neither HPV nor EBV PCR products was detected in both OVC and OVH samples. Conclusions In summary, our study demonstrated that HPV and EBV are not involved in pathogenesis of OVC and OVH. Other etiologic factors contributing to OVC and OVH need to be further clarified.

Loss of TACC1 variant25 inducing cell proliferation and suppressing autophagy in head and neck squamous carcinoma

Transforming acidic coiled-coil containing protein1 (TACC1) is closely related to transcription, translation and centrosome dynamics. Dysregulation of TACC1 is associated with multiple malignancies. Alternative splicing (AS) of TACC1 produces multiple variants, which are of great significance in cancer biology. However, the expression and biological functions of TACC1 variants in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we found for the first time that TACC1 variants exhibited a characteristic expression pattern and that TACC1 variant25 (TACC1v25) was downregulated in HNSCC tissues and cell lines. Overexpression of TACC1v25 in Cal27 and Fadu cells significantly inhibited proliferation and promoted autophagy. Moreover, expression levels of nuclear pERK and p-mTOR were significantly decreased, while the expression of Beclin-1 and the LC3II/LC3I ratio were increased in TACC1v25-overexpressed Cal27 and Fadu cells. After the addition of AKT activator SC79 to TACC1v25-overexpressed Cal27 and Fadu cells, the autophagy levels were remarkably rescued. In conclusion, TACC1v25 inhibits HNSCC progression through the ERK and AKT/mTOR pathways by inhibiting proliferation and increasing autophagy. TACC1v25 might have potential use as a tumour suppressor in HNSCC.

Acantholytic squamous cell carcinomas of the cervix: A case series

Squamous cell carcinoma of the uterine cervix is considered the most common histologic variant of cervical cancer, with well-established treatment protocols and prognosis. An infrequent histologic variant of cervical squamous cell carcinoma is the acantholytic variant (ASCC), which is characterized by discohesive cells that result in a pseudoglandular and/or angiomatoid pattern of growth. This variant of squamous cell carcinoma has been regarded as having a poor prognosis at certain anatomic sites such as the head and neck and vulva. In the uterine cervix, the importance of this variant has not been yet established. A ten-year retrospective review of squamous cell carcinoma of the uterine cervix was performed to identify this variant and correlate it with clinical characteristics to better define its prognostic implications. During the study period 19 cases were identified containing from 10 to 80% acantholytic component. Mean age at diagnosis was 49 years. Clinical stages were 1A2 (1 case), Ib1 (16), and IIA1 (2). Median follow-up was 92 months. When compared with controls, ASCC were larger in size (1.4 vs 3.5 cm), had deeper involvement of the cervical stroma (21 vs 47%), had more lymph node metastasis (8 vs 26%), more frequent recurrences (4 vs 15%) and a shorter disease-free survival; however, no statistical differences were identified in overall survival. ASCC is an infrequent variant of cervical cancer which seems to have an impact on disease-free survival but no in overall survival.

Potential role of immune cell genetic variants associated with tumor microenvironment response in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features

Immunomodulatory signals regulate the self-tolerance, activation, priming and survival processes of T cells. Programmed cell death protein 1 (PD1), Programmed death-ligand 1 (PD-L1) inhibitory signals and CD27, CD28 costimulators have been detected for many solid organ cancers in tumor-infiltrating T cells. It was aimed to investigate the immune cell-based regulatory genetic variants in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features. Genotyping was performed by PCR-RFLP method for PD-1 rs2227981, PD-L1 rs2890658, CD28 rs3116496, CD27 rs2267966 genetic variants from genomic DNAs extracted from peripheral blood samples in One Hundred Thirty-Six individuals (Sixty-one LSCC and seventy-five controls). Analysis of SNPs was carried out according to multiple inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). There was no difference between LSCC and control groups in genotype/allele distribution for PD-1 and PD-L1 (p > 0.05). In the PD-1 overdominant model, the CT genotype was found to be high (p = 0.036) in those without a family history. The frequency of C allele (AC+CC) in the PD-L1 dominant model was higher in alcohol users and those with reflux (p = 0.024; p = 0.001 respectively). In the Dominant model for PD-L1, the AA genotype was lower in moderately and well-differentiated tumors than in poorly differentiated tumors (p = 0.02). CD27 AT and CD28 CT genotypes were found to be higher in LSCC patients compared to the control group (p = 0.009; p = 0.01 respectively), while linkage disequilibrium (LD) was detected between CD27 and CD28 (p = 0.02). In the CD28 dominant model, C allele (CT+CC) carriage was found to be high in those with family history and in those without reflux and perineural invasion (p = 0.01; p = 0.01; p = 0.03 respectively). In LSCC, PD-L1 rather than PD-1 has a prognostic effect in terms of clinicopathology, and the LD and clinicopathological relationships detected between CD28 and CD27 genotypes suggest that the hereditary immune checkpoint-dependent T cell traffic may be pathophysiologically important.