الفهرس | Only 14 pages are availabe for public view |
Abstract Worldwide, breast cancer is the most prevalent cancer in females with estimated number of 2.261.419 new cases in 2020. It represents 24.5% of all cancers that affect females in the world. In Egypt, breast cancer is the most common malignancy in women, accounting for 32.4% of cancers with the estimated number of breast cancer cases nearly 22.038 in 2020. The aim of this study is to evaluate immunohistochemical expression ofRCC2, Rac1 and p53 in primary breast invasive duct carcinoma and corresponding metastatic sites and correlation of the results with the available clinicopathological parameters. Using the standard IHC technique, we assessed RCC2, Rac1 and p53 expressions in 120 breast cancer specimens. Eighty one cases with corresponding positive lymph nodes and thirty nine cases without lymph nodes metastasis. This selective cross-sectional retrospective study included 120 primary breast infiltrating duct carcinoma (IDC), NOS specimens from Egyptian patients retrieved from archival material in pathology Department, Faculty of Medicine, Menoufia University spanning the period between January 2018 and December 2020. In this study, patient’s age ranges from 27– 75 years with a mean ± SD of 51.37 ±10.82 and a median of 50.5. More than half of cases (68/120, 56.7%) were postmenopausal. Left breast was involved in sixty percent (72/120) of cases. The majority of cases were presented as single mass (102/120, 85%). Tumor size ranges from 1 – 15 cm with mean ± SD of 3.68 ±1.95 and a median of 3.5. Most of cases were of grade 2 (105/120, 87.5%). Fifty eight (48.3%) cases showed DCIS component and 38 of them (38/58, 65.5%) were comedo pattern. Only 35 cases Summary 204 showed necrosis (29.2%). Mitotic figures count ranges from 1 – 5 mitoses/10 HpF with mean ±SD of 1.34 ±0.68 and a median of 1. Apoptotic bodies count ranges from 2 – 9 apoptotic bodies / 10 HpF with mean ± SD of 3.08 ± 1.47 and a median of 3. Sixty seven cases showed low TILs (55.8%), 20 cases showed intermediate TILs (16.7%) and 33 cases showed high TILs (27.5%) Thirteen cases showed LVI (10.8%). Seventy cases were of pT2 (58.3%), while 26 cases (21.7%) and 24 cases (20%) were of pT1 and pT3, respectively. Thirty nine cases were of N0 (32.5 %), 43 of N1 (35.8%) while 24 cases (20%) and 14 cases (11.7%) were of N2 and N3, respectively. NPIs ranges from 2.8 – 8 with mean ± SD of 4.79 ± 0.98 and a median of 4. Eighty cases (66.7%) showed positive ER. Fifty eight cases (48.3%) showed positive PR. Twenty five cases (20.8%) showed positive Her2neu. Most of cases (73/120, 60.8%) showed >14% Ki67 expression. Sixty seven cases (55.8%) were luminal A, 22 were luminal B (18.3%), 3 were Her2neu enriched (2.5%) and 28 were triple negative (23.4%). As regards RCC2 expression, the majority of cases showed positive RCC2 expression (116/120, 96.7%). Sixty three cases showed low expression (≤ 40%) (52.5%) and 57 cases showed high expression (>40%) (47.5%). RCC2 percentage of expression ranged between 0 – 90 with mean ± SD of 43.67 ± 22.3 and a median of 40. Regarding intensity of expression, four cases were negative (3.3%), eight cases were mild (6.7%), 47 cases were moderate (39.2%) and 61 cases showed strong intensity of expression (50.8%). In the present study, N +ve IDC showed positive expression of RCC2 in 78/81 cases (96.3%). Low RCC2 expression (≤ 40%) was observed in more than half of nodal +ve IDC (56.8%). RCC2 percentage of expression in N +ve IDC ranged between 0– 90 with mean ± SD of 42.96 ± 22.33 and a median of 40. Regarding Summary 205 RCC2 intensity in N +ve IDC, three cases were negative (3.7%), 7 cases were mild (8.6%), 36 cases were moderate (44.4%) and 35 cases showed strong intensity of expression (43.3%). Corresponding +ve LNs showed positive expression of RCC2 in 79/81 cases (97.5%). Low RCC2 expression (≤ 40%) was observed in more than half of corresponding +ve LNs (51.9%). RCC2 percentage in corresponding +ve LNs ranged between 0 – 90 with mean ± SD of 43.46 ± 21.34 and a median of 40. Regarding RCC2 intensity in corresponding +ve LNs, two cases were negative (2.5%), 7 cases were mild (8.6%), 32 cases were moderate (39.5%) and 40 cases were strong intensity of expression (49.4%). As regards RCC2, high expression, percent and intensity showed significant association with frequent mitoses (p =<0.001 and <0.001 respectively), high apoptotic count (p=<0.001, <0.001 and 0.042 respectively), high Ki67 (p=<0.001 and <0.001 respectively), LVI (p=0.024 and 0.03 respectively). There was a near significant association between low RCC2 expression and advanced nodal stage (p=0.057). High RCC2 percent and strong RCC2 intensity showed a significant association and positive Her2neu (p=0.012 and 0.017 respectively) and molecular subtypes (p=0.012 and 0.021 respectively). A statistically significant correlation in the percent of RCC2 in the primary breast tissue versus metastatic lymph node specimens (r= 0.29, p= 0.008). As regards Rac1 expression, all studied cases showed Rac1 positive expression (100%). Sixty four cases showed low expression (≤ 30%) (53.3%) and 56 cases showed high expression (>30%) (46.7%). Rac1 percentage of expression ranged between 10 –70 with mean ± SD of 31.0 ± 16.97 and a median of 30. Regarding intensity of expression, 36 Summary 206 cases were mild (30%), 40 cases were moderate (33.3%) and 44 cases showed strong intensity of expression (36.7%). In the present study, N +ve IDC showed positive Rac1 expression (100%). High Rac1 percentage of expression (>30%) was observed in 41 cases of nodal +ve IDC (50.6%). Rac1 percentage of expression in N +ve IDC ranged between 10 -70 with mean ± SD of 31.85 ± 17.40 and a median of 40. Regarding N +ve IDC, twenty five cases were mild (30.9%), 27 cases were moderate (33.3%) and 29 cases showed strong intensity of expression (35.8%). Corresponding +ve LNs showed positive expression of Rac1 in 72/81 of cases (88.9%). High Rac1 percentage of expression (>30%) was observed in 45 cases of their corresponding +ve LNs (55.6%). Rac1 percentage of expression in corresponding +ve LNs ranged between 0 – 60 with mean ± SD of 32.22 ± 18.10 and a median of 40. Regarding their corresponding +ve LNs, nine cases were negative (11.1 %), 14 cases were mild (17.3%), 26 cases were moderate (32.1%) and 32 cases were strong intensity of expression (39.5%). As regards Rac1, high expression, percent and intensity showed significant association with high Ki67 status (p=<0.001 and <0.001 respectively), molecular subtypes (p=0.009 and 0.010 respectively), frequent apoptosis (p=0.019 and 0.003 respectively), presence of LVI (p=0.021 and 0.036 respectively), positive ER (p=0.028 and 0.022 respectively), positive PR (p=0.030) and positive Her2neu (p=0.016, 0.013 and 0.036 respectively). There was a near significant association between high Rac1 expression and older age (p=0.054) and large tumor size (p=0.057). There was a significant association between moderate/ strong Rac1 intensity and frequent mitoses (p=0.047). Summary 207 A regards p53 expression, the majority of cases showed negative p53 expression p53 (87/120, 72.5%) and 33 cases (27.5%) were positive. p53 percentage of expression among positive cases ranged between 5 – 50 with mean ± SD of 22.73 ± 16.35 and a median of 20. Regarding intensity of expression, eight cases were mild (24.2%), 5 cases were moderate (15.2%) and 20 cases were strong (60.6%). Nodal +ve IDC showed negative expression in (58/81, 71.6%) and positive expression of p53 in (23/81, 28.4%). p53 percentage of expression in N +ve IDC ranged between 5– 50 with mean ± SD of 22.17 ± 15.65 and a median of 20. Regarding N +ve IDC, five cases were mild (21.7%), 4 cases were moderate (17.4%) and 14 cases showed strong intensity of expression (60.9%). Corresponding +ve LNs showed negative expression in (58/81, 71.6%) positive expression of p53 in (23/81, 28.4%). p53 percentage of expression in corresponding +ve LNs ranged between 5– 50 with mean ± SD of 23.48 ± 16.41 and a median of 20. Regarding their corresponding +ve LNs, six cases were mild (26.1%), 6 cases were moderate (26.1%) and 11 cases showed strong intensity of expression (47.8%). As regards p53, significant association was found between positive p53 expression and increased tumor size (p=0.009), high TILs (p=0.008), high Ki67 status (p=0.001) and Apoptosis (p=0.013). On the other hand, there was a significant inverse relation between p53 percent and strong p53 intensity and PR status (p=0.041 and 0.002 respectively). There was a highly significant association between strong p53 intensity and early nodal stage (N0+N1) (p=0.009). There was a near significant relation between strong p53 intensity and high tumor grade (grade 3) (p=0.060) and absence of in situ component (p= 0.055). A statistically significant Summary 208 correlation in the percent of p53 in the N+ve IDC versus corresponding metastatic lymph node specimens (r= 0.32, p= 0.003). There was a highly significant direct correlation between each marker in this study and the other 2 markers (p= <0,001, <0.001 and 0.006). As regards survival data, Twenty three cases (28 %) have positive family history. Four cases had cardiac disease (4.9 %), six cases had Hepatitis C virus +ve (7.3 %), seven cases had Diabetes Mellitus (8.5%), thirteen cases had Hypertension (15.9%) and four cases had both Hypertension and Diabetes Mellitus (4.9%). Thirteen cases showed metastasis to distant organs (15.9%). 25 cases were having gross disease during received treatment, 13 cases (52%) showed progressive disease (pD), 9 cases (36%) showed partial response (pR), two cases (8%) showed stationary disease (SD) and one cases (4%) showed complete response (CR). Seventy five cases were alive (75/81, 91.5%) and seven cases were dead (7/81, 8.5%). PFS ranged between 6 – 52 months with a mean ±SD of 31.87 ± 13.37 and a median of 35 months. OS ranged between 11 and 52 months with a mean ±SD of 34.93 ± 10.60 and a median of 37 months. As regards response to treatment, significant association between progressive disease and low TILs (p= 0.009), advanced tumor stage (T3) (p=0.002), metastatic status (p=<0.001), dead patients (p= 0.005), and short OS (p<0.001), larger tumor size (p=0.011) and short PFS (p=0.011). As regards distant metastatic status, significant association between positive distant metastatic status and large tumor size (p=0.003), higher NPIs (p=0.007), progressive disease (p<0.001), death of patients Summary 209 (p<0.001), short PFS (p<0.001), positive Her2neu status (p=0.023) and short OS (p=0.024). As regards PFS, significant association between shorter progression free survival and advanced tumor stage (T3) (p=0.001), presence of metastasis to distant organs (p<0.001) and progressive disease (p<0.001), positive Her2neu status (p=0.011) and Luminal B molecular subtypes (p=0.023). Multivariate analysis for the parameters affecting progression free survival revealed that presence of metastasis to distant organs was the most independent factor affecting progression free survival (p=0.001). As regards OS, significant association between shorter overall survival in patients presented by multifocal tumors (p=0.017), advanced tumor stage (T3) (p=0.010) and Luminal B cases (p=0.015), progressive disease (p=0.003), positive Her2neu status (p=0.008) and presence of metastasis to distant organs (p<0.001). Results of RCC2, Rac1 and p53 immunostaining showed a non-significant relation to response to treatment, distant metastatic status, PFS or overall survival. |