IRANIAN JOURNAL OF PATHOLOGY (IJP)
Year:2024 | Volume:19 | Issue:1|Papers Count:16

The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10–30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that the inhibition of proprotein convertase subtilisin/Kexin type 9 (PCSK9), which plays a critical role in regulating cholesterol metabolism, can cause T cells to move toward tumors, with increased sensitivity to immune checkpoint therapies.We searched PubMed, NCBI, Scopus, and Google Scholar for the published articles without limitations on publication dates. We used the following terms: “PCSK9”, “Cancer”, “Immune Checkpoint”, and “Cancer Prognosis” in the title and/or abstract. Our search initially revealed 600 records on the subject and stored them in the used databases under EndNote X8 management software. We selected about 161 articles that were carefully read and among them, 76 were included in our research.We concluded that PCSK9 reduces the number of LDL receptors (LDL-R) on the cell surface, which is linked to its ability to regulate cholesterol levels in the body. Also, we discuss how suppressing PCSK9 leads to the MHC-1 accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK9 may be an effective strategy for improving cancer immunotherapy.

Background: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that can carry fatty acids to many organelles. Subunit 2 of the GINS complex (GINS2), which belongs to the GINS complex family, encodes a protein that initiates DNA replication and controls the cell cycle and normal cell division. Chromobox homolog 7 (CBX7) was found to promote cancer occurrence and spread through the promotion of EMT.Objective: The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cancer cervix tissue to detect their prognostic and predictive roles in the development of lymph node metastases in cancer cervix patientsMethods: we collected tissues from patients with cancer cervix and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters.Results: high expression of FABP4 and GINS2, in addition to low expression of CBX7, was positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence.Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results indicated that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer cervix preoperatively, which could be beneficial in the accurate preoperative design therapy.

Background & Objective: Colorectal carcinoma (CRC) is one of the most common cancers worldwide. The interaction of programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) plays an important role by inhibiting the immune mechanism by which cancer cells escape antitumor immunity. Immunotherapy using checkpoint inhibitors is a growing treatment modality in many cancers; one such is anti-PD1/PD-L1. The present study aimed to study the immunohistochemical (IHC) expression of PD-L1 in CRC and evaluate the association of PD-L1 expression in CRC with various known clinicopathological parameters.Methods: It was a 2-year prospective study and included 34 colectomy specimens diagnosed as colorectal adenocarcinoma. The expression of PD-L1 was evaluated on tumor cells & tumor-infiltrating immune cells (TIICs) and correlated with various clinicopathological parameters.Results: Immunohistochemical expression of PD-L1 on tumor cells and tumor microenvironment in CRC revealed positivity in 17.65% of cases each. The PD-L1 expression on tumor cells was associated with lymphovascular invasion (LVI) and perineural invasion (PNI) with P- values of 0.012 and 0.005, respectively, while PD-L1 expression on TIICs was associated with tumor budding with P-value 0.022.Conclusion: IHC expression of PD-L1 on tumor cells and immune cells was associated with some known poor prognostic factors. Since anti-PD1/PD-L1 is used for targeted therapy, it may be beneficial and economically feasible to evaluate PD-L1 in CRC and establish its role as a prognostic factor.

Breast cancer is one of the common malignant tumors worldwide accounting for 15% of all cancer-related deaths. Since a timely diagnosis of BC is essential for optimal treatment and also increasing the survival rate of patients. Today, various financial support is applied to find the best biomarkers. Considering the financial issue, in-silico analysis is the best approach. LRP family proteins are important components of cell-surface receptors that involved in numerous biological activities. One of the most pivotal role LRPs is Wnt signaling pathway. Expression of LRP is related with BC malignancy. In this study, we first investigated expression of LRPs in BC tissues in comparison with normal tissues. Relation of LRP expression with RFS and OS. Then, we investigated the association of LRPs expression and immune infiltrating abundance.

Background & Objective: Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was conducted to investigate the immunohistochemical overexpression of p16, a surrogate marker for HPV, and to evaluate its usefulness as a potential diagnostic biomarker.Methods: In this cross-sectional prospective and retrospective cohort study, 56 penile squamous cell carcinoma (SCC) specimens and five penile premalignant specimens were evaluated in Kasturba Medical College, Mangalore, India, from January 2013- December 2018 in terms of clinical and histopathological features. Immunohistochemical expression for p16 in cases and controls was evaluated. Statistical comparison of p16 expression among clinical features, histological subtype, grade, and stages of tumor were done.Results: Analysis of the pattern of p16 staining showed diffuse and strong nuclear and cytoplasmic expression in 32.8% of cases. There was a highly significant association (P<0.001) of pattern of p16 expression among the HPV and non-HPV subtypes of penile carcinoma. p16 expression was not significantly associated with other prognostic parameters like the site of lesion, lymphovascular invasion, perineural invasion, histologic grade, and pathologic stage.Conclusion: The expression of p16 would be a useful tool in the discrimination between the HPV-associated and non-HPV-associated subtypes of penile SCC that helps to predict the aggressiveness and invasive potential of the respective histologic subtypes.

Background & Objective: Colorectal cancer is the second reason for cancer-associated death. The prognosis of the malignancy is defined by TNM scoring. However, tumor grading, lymphovascular invasion, perineural invasion, and tumor buddings may affect its prognosis. This study aimed to assess the prognostic and histologic impact of tumor budding in colorectal adenocarcinoma.Methods: This study is a retrospective cohort of 192 patients with colorectal adenocarcinoma. All four stages of colorectal adenocarcinoma patients were included, but the patients in stages I and II were also analyzed separately. We used pathology reports to extract the histopathologic data. The prognostic values were extracted by calling the patients.Results: Less than half of the patients were in stages I and II of the disease. According to our analysis, tumor extension and lymphovascular invasion were correlated with tumor budding count in patients in stages I and II, and lymphovascular invasion, tumor grade, tumor stage, lymph node involvement, tumor extension, tumor site, metastasis, and five-year survival were correlated with tumor budding within all stages.Conclusion: It is recommended that tumor budding count should be assessed and reported in pathology reports of adenocarcinomas due to its high correlation with poor prognosis.

Background & Objective: Breast cancer recurrence after surgery was a sign that the progress of the disease was continuing. Early detection of breast cancer patients who are at risk requires  development of a marker. Alfa smooth muscle actin (α-SMA) plays a role in the local recurrence process of invasive ductal carcinoma (IDC). Currently, existing tumor markers are used to predict the prognosis of breast cancer in general, not the early stages. Therefore, it was thought that finding α-SMA expression might predict early recurrence in early-stage IDC more accurately than others. This study investigated the potential role of α-SMA expression as a predictor of early recurrence in early-stage IDC and its relationship to clinicopathological factors.Methods: The study design was cross-sectional, with data obtained from the medical records of Dr. Koesnadi, General Hospital, Bondowoso, Indonesia. Bivariate and multivariate analysis was performed to analyze data.Results: We included 50 subjects divided into the local recurrence group (n=25) and the non-local recurrence group (n=25). We found a statistically significant correlation between the incidence of local recurrence in early-stage IDC and the high expression of α-SMA (odd ratio [OR]=23.22, 95% confidence interval [CI]=5.101-105.7, P=0.001). Clinicopathological variables and α-SMA expression did not have a significant correlation.Conclusion: In early-stage IDC, α-SMA expression had the potential to predict and could be an independent prognostic factor for early recurrence.

Background & Objective: An accurate Ki-67 labeling index assessment is critical for managing a few tumors, like breast carcinomas and neuroendocrine tumors. We aimed to determine the degree of agreement between digital image analysis (DIA) & eye-rolling assessment (EE) and DIA & manual count (MC) for Ki-67 LI scoring.Methods: A total of 120 cases (Both tru-cut biopsies and resected specimens) were selected during the study period from the institutional database wherein the Ki-67 labeling index was performed. The selected cases were divided into two groups, i.e., breast neoplasms and other neoplasms. The correlation between DIA & EE and DIA & MC for Ki-67 LI scoring was calculated in both groups.Results: A total of 113 cases were analyzed for Ki-67 LI by three different methods (EE, MC, & DIA); 7 cases were rejected because of poor image quality. Ki-67 LI scoring by DIA & EE was highly correlated in both the study groups with a Spearman's rank correlation coefficient of 0.809 (P=0.01) and 0.904 (P=0.01), respectively. Correlation between DIA & MC methods was also found to be almost perfect in both study groups with a Spearman's rank correlation coefficient of 0.974 (P=0.01) and 0.955 (P=0.01), respectively.Conclusion: ImmunoRatio is a free web-based digital image analysis application that can be used for Ki-67 LI assessment with considerable reliability and reproducibility. Yet, it carries a few limitations and demands a careful approach and final confirmation by an expert.

Background & Objective: Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been linked to some malignancies in humans. The aim of this study is to analyze the clinicopathological data of patients while investigating FGFR2 and FGFR3 immunohistochemical expression in invasive urothelial bladder carcinoma.Methods: This retrospective cross-sectional study included 60 invasive urothelial carcinoma (UC) cases in the Pathology department, Faculty of Medicine, Menoufia University, from 2009 to 2020. All biopsies were stained for FGFR2 and FGFR3 antibodies. Complete clinical data were available for 44 patients treated and followed in clinical oncology and nuclear medicine departments.Results: Advanced stage and high grade are significantly correlated with FGFR2 positivity (P=0.048 and 0.044, respectively). Cases presented with Perineural invasion showed a higher percentage of FGFR2 (P=0.023). There is a significant indirect linear correlation between FGFR3 expression and lymph node positivity (r= -0.265, P=0.041).Conclusion: High FGFR2 expression was associated with poor prognostic parameters, while high FGFR3 expression was associated with good prognostic parameters, and this might highlight the importance of FGFR-targeted therapy as FGFR2 antagonist and FGFR3 agonist for the treatment of urothelial carcinoma patients.

Background & Objective: Colorectal carcinoma (CRC) is the third leading cause of cancer-caused death worldwide and constitutes about 6.48% of all malignancies in Egypt. Studying the molecular profile of CRC is essential for developing targeted therapies. STAT3 and CTLA4 expression are among the molecular abnormalities claimed to cause CRC progression and chemo-resistance. Therefore, they could be used as potential therapeutic targets. This study aimed to evaluate pSTAT3 and CTLA4 expression levels and their possible roles as prognostic and predictive biomarkers in CRC using immunohistochemistry (IHC).Methods: This retrospective study included 113 CRC patients. Tissue microarrays were constructed, followed by pSTAT3 and CTLA4 antibodies immunostaining. Their expression was assessed and compared with clinicopathological parameters and survival data.Results: Both pSTAT3 and CTLA4 overexpression were significantly associated with poor prognostic parameters, such as the presence of distant metastasis (P=0.02 & 0.03), high grade (P<0.001 & 0.03), high mitotic count (P<0.001 & 0.03), high tumor budding group (P=0.008 & 0.04), infiltrating tumor border (P<0.001 & 0.007) respectively, and advanced pathological stage with pSTAT3 (P=0.02). A significant association was found between overexpression of both markers and short overall survival. Correlations between the H-score of pSTAT3 and CTLA4 in CRC showed a significant positive correlation (P<0.001).Conclusion: STAT3 and CTLA4 positivity have been linked to the development and progression of CRC, and they may provide potential prognostic indicators and therapeutic targets for CRC patients.

Background & Objective: Antigen Ki-67 (histone-based nuclear protein) is a static marker of tumor cell proliferation and growth and is commonly measured to indicate the effect of treatment in breast cancer patients. This single-arm trial study aimed to evaluate the effect of short-term endocrine therapy (letrozole) on Ki-67 levels in menopausal women with early hormone-positive breast cancer who were referred to two university hospitals.Methods: Patients with a pre-treatment Ki67 of 5% or less were excluded from the study. Participants (n=25) received oral letrozole (2.5 mg daily) seven days before surgery. Ki-67% on both the biopsy and the surgical specimens were measured and compared.Results and Conclusion: The mean age of patients was 62±9.4 (48-83 years). Our result indicated that consumption of letrozole before surgery for hormone-positive breast cancer can significantly decrease the level of Ki-67 (23.24±9.74 vs. 16.92±9.55, P=0.001 by paired t-test), with no drug-related adverse events.

Sclerosing microcystic adenocarcinoma (SMA) is an uncommon neoplasm of the oral cavity, with only 14 reported cases documented in the literature.We present a case of SMA in a 65-year-old woman with a history of high-grade lymphoma who developed clear cell changes in the deep muscular layer of the tongue.Currently, the diagnosis of SMA relies on careful morphological evaluation and the exclusion of other potential differential diagnoses.

Malignant melanoma of the small intestine is mostly a metastatic tumor of other primary lesions, especially of skin origin. Primary malignant melanoma of the small intestine is very uncommon. The clinical presentation is usually nonspecific, thus leading to late diagnosis.We report a 42-year-old man who presented to the emergency department of Imam-Reza Hospital with symptoms and signs of peritonitis and was a candidate for emergency laparotomy and enterectomy. The medical and family history were unremarkable. A bulky mass was seen, 190 cm away from the Treitz band, and a diagnosis of malignant melanoma was confirmed by histologic and immunohistochemical study. Further clinical examination revealed no primary tumor elsewhere, so the diagnosis of primary small intestinal melanoma was concluded.Although metastatic malignant melanoma in the GI tract is common, the primary one is a very rare entity. The diagnosis could be challenging because a thorough investigation is needed to rule out the possible initial origin.

Background: Breast sarcoma is a rare, but aggressive tumor. There are few case reports in the literature and several aspects of this disease are still not completely comprehended. Therefore, reporting new cases can help to enrich the literature.Case Presentation: We report a case with a breast mass and pus secretion from her right breast, misdiagnosed as having an abscess and mistreated by antibiotics. The patient was referred for an ultrasound examination and mammography, and a needle biopsy was performed that suggested an aggressive tumor. By the pathologist’s suggestion, a total mastectomy of the right breast was performed with the excision of sentinel nodes. A pathological examination revealed high-grade undifferentiated pleomorphic sarcoma (UPS) without vascular or lymph node invasion as the final diagnosis. The patient underwent postoperative chemotherapy and is currently in good condition.Conclusion: This case emphasizes considering this rare tumor when approaching a breast mass. Performing surgery with adequate resection margin can improve the patient’s prognosis. Some cases reporting lung and brain metastasis suggest breast UPS is a more aggressive tumor than other breast sarcomas. Total mastectomy with negative margins and free-of-tumor lymph nodes may be the key to improved prognosis in such patients.

BackgroundCovid-19 in known to present with acute respiratory distress syndrome pathological manifestations. Studies have shown that patients with Covid-19 can develope diffuse alveolar damage, acute bronchopneumonia, necrotic bronchiolitis, and viral pneumonia.Case PresentationIn this study, we investigate 11 cases. Needle necropsies of 11 patients, hospitalized at Tohid and Kowsar hospitals of Kurdistan University of medical Sciences, with a positive antemortem SARS-CoV-2 (COVID-19) real time PCR test, were fixated within 3 hours after death in the negative-pressure isolation morgue. The participants included 6 men (54%) and 5 women (46%) with mean age of 73.82 ± 10.58 (52–86) years old. The average hospitalization was 14.27 ± 15.72 days. The results showed an interstitial lymphocytic pneumonitis in most of the cases, with severities ranging from mild to moderate and severe in some cases. In 7 cases, Anthracosis and in one case, anthracosis with fibrosis was evident. Hyaline membrane was reported in two patients. In one case, a severe interstitial lymphocytic pneumonia with intra-alveolar exudate with organization, lithiasis, bronchiolitis pattern (BOOP) along with intra-alveolar hemorrhage and mild fibrosis was seen.ConclusionAs a result, it is suggested to keep an eye on these pathologies in managing severe case of COVID-19 infection.

The occurrence of rectosigmoid junction inflammatory myofibroblastic tumor IMT is uncommon in children. This is a rare form of mesenchymal tumor, belonging to the category of soft tissue tumors, and can be found at any anatomical site from the central nervous system to the gastrointestinal tract.Our patient was a 10-year-old male subject complaining of lack of defecation and constipation. The patient had decreased the frequency of defecation and constipation about two weeks before his referral and had not improved despite the use of laxatives. The abdomen was completely distended and there was no tenderness or guarding in the examination. Several airfluid levels are shown on the abdominal X-ray. In the ultrasound, free fluid was reported in the interlobular and pelvic spaces. The patient was transferred into the operating room. A tumor of the rectosigmoid junction was detected. The pathology showed evidence of IMT.IMT is a rare neoplastic tumor of unknown origin which may be present at various sites in the body. Complete surgical removal is usually curative, but early detection of recurrence is required. Treatment options include chemotherapy, radiation therapy, and immunotherapy, and further research is needed to improve the understanding and management of this rare tumor.