Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters.

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

INTRODUCTION:  Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC). Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters. METHODS:  This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought. RESULTS:  p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression. CONCLUSION:  Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features.

Luminal B, Human Epidermal Growth Factor Receptor 2 (HER2/neu), and Triple-Negative Breast Cancers Associated With a Better Chemotherapy Response Than Luminal A Breast Cancers in Postneoadjuvant Settings.

Background Breast cancer is a heterogeneous disease with many histological and molecular/intrinsic breast cancer subtypes. Intrinsic breast cancer subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2/neu), and triple-negative subtypes. The intrinsic breast cancer typing is based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki67-labeling index. One of these patients' foremost prognostic factors upon surgical resection is a response to neoadjuvant chemotherapy. The presence of a pathologically complete response (pCR) indicates a favorable patient outcome compared with a pathologically partial response (pPR). In this study, we compared the neoadjuvant chemotherapy response in breast cancer in different intrinsic breast cancer subtypes. Methodology It was a retrospective cross-sectional study conducted in the Department of Histopathology, Liaquat National Hospital, from January 2019 to December 2022, over three years. A total of 287 post-neoadjuvant chemotherapy cases of breast cancer were included. Anthracyclines and taxanes, coupled with or without anti-HER2/neu therapy, have been used in the neoadjuvant chemotherapy treatment setting contingent upon the patients' HER2/neu status. The post-chemotherapy response was assessed pathologically and categorized into pCR and pPR. Results The mean age of the patients was 47.90 ± 10.34 years, with a mean tumor size and Ki67 index of 5.36 ± 2.59 cm and 36.30 ± 22.14%, respectively. Invasive breast carcinoma of no special type (IBC-NST) made up 88.2% of cases, while grade 2 carcinomas made up 45.5%. The majority of tumors (42.7%) belonged to tumor (T) stage T2, and nodal metastasis was detected in 59.7% of patients. The intrinsic breast cancer subtypes luminal B (40.6%) and triple negative (33.3%) were the most prevalent, followed by luminal A (15.8%) and HER2/neu (10.3%). In 81 cases (24.5%), pCR was detected. The association of post-neoadjuvant chemotherapy response with intrinsic breast cancer subtypes showed a significant difference (P < 0.001). The highest frequency of pCR was noted in HER2/neu cancers (58.8%), followed by luminal B (25.4%) and triple negative (23.6%). Regarding age, T-stage, tumor grade, and histological type of carcinoma, there was no discernible difference between pCR and pPR. Conversely, a significant association was noted for the Ki67 index. A Ki67 index higher than 25% showed a significantly higher frequency of pCR. Conclusions In postchemotherapy specimens, the HER2/neu breast cancer subtype substantially displayed higher pCR, followed by luminal B and triple-negative subtypes. After identifying the patients' subtypes, intrinsic subtyping can help determine the prognosis and anticipated response to chemotherapy. Furthermore, prechemotherapy breast specimens with high Ki67 index values have shown a direct association with neoadjuvant chemotherapy response.