Mutant-type P53 Expression Research Articles

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

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. 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. 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. 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.

The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes.

Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p < 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.

Independent validation of distinct clinicopathological features and prognosis among usual-type, mucinous-type and gastric-type endocervical adenocarcinoma categorised by new WHO classification (2020)

The new World Health Organization (WHO) classification of tumours of the female genital tract (2020) divides endocervical adenocarcinoma (EAC) into human papilloma virus (HPV)-related adenocarcinoma (HPVA) and HPV-independent adenocarcinoma (HPVI) to underscore the morphological and pathogenetic correlation. It may be potentially prognostic. In this study, we appraised the new WHO classification in an independent, single institution-based EAC cohort from China to assess the clinicopathological features and prognostic value among tumour types. Our study cohort contained 402 consecutive, surgically excised EACs consisting of 298 (74.1%) HPVA, 88 (21.9%) HPVI and 16 (4%) adenocarcinomas not otherwise specified (NOS). Usual-type (55.7%) and gastric-type adenocarcinoma (GAC) (18.2%) was the most common type in HPVA and HPVI, respectively. Block p16 staining (94.7% vs 24.4%) and HPV mRNA signal (89.4% vs 0) were more common in HPVA than in HPVI (p<0.001). HPVI or GAC were more frequently associated with prognostically adverse variables including old age, large tumour size, deep invasion of the cervical wall, high tumour stage, spread of the upper genital tract, lymphovascular invasion, and mutant-type p53 expression, compared to HPVA or mucinous/usual-type HPVA, respectively (all p<0.001). In univariate survival analysis, HPVI had a worse overall survival and higher tumour recurrence compared to HPVA (p<0.05). Mucinous-type HPVA showed a worse prognosis than usual-type HPVA, but better than GAC (p<0.001). Multivariate survival analysis demonstrated that HPVI was independently associated with a worse overall survival and tumour recurrence (p<0.05) while GAC was an adverse prognostic factor independently of FIGO stage (p<0.05). Our findings validate the value of the new WHO classification in prognostic stratification and pathogenetic correlation in EAC and its subtypes.

Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma.

TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada. Mutant-type p53 expression, including overexpression, complete absence, or cytoplasmic expression, was distinguished from the wild-type pattern. Statistical associations with clinico-pathological parameter, other key biomarkers, and survival analyses were performed. P53 mutant-type immunohistochemistry was observed in all 126 ESC and in 47/200 (23.5%) EEC3. ESC and p53 mutated EEC3 had an unfavorable outcome compared with p53 wild-type EEC3 (hazard ratio=2.37, 95% confidence interval=1.48-3.80, P=0.003, hazard ratio=2.19, 95% confidence interval=1.16-4.12, P=0.016, respectively) in multivariable analyses adjusted for age, stage, center, and presence of lymph-vascular invasion. There was no significant difference in survival between ESC and p53 mutated EEC3 in multivariable analysis. Furthermore, p53 mutated EEC3 and ESC almost completely overlapped in univariate survival analysis when mismatch repair (MMR)-deficient cases were excluded, which suggests that EEC3 harboring combined MMR deficiency and TP53 mutations behave more according to the MMR status. Significant differences between p53 mutated MMR-proficient EEC3 and ESC in PTEN and p16 expression status remained. p53 mutated, MMR-proficient EEC3 and ESC have overlapping survival significantly different from p53 wild-type EEC3, which justifies a similar treatment with current non-targeted standard therapy. Although this is so, separate classification should continue due to biological differences that will become important for future targeted therapy.

Legumain protein as a potential predictive biomarker for Asian patients with breast carcinoma.

Treatment for breast cancer is mainly performed by surgical resection of primary tumors and chemotherapy. However, after tumor invasion and metastases, breast cancer is hard to control. Clarification of the pathogenic mechanisms would be helpful to the prognosis or therapy for the breast cancer. The aim of this study is to investigate the clinical and prognostic implications of legumain protein Materials and Methods: In this study, we examined mastectomy specimens from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using immunohistochemistry. The results indicated that positive expression of legumain protein in breast cancer was 51.8 % (59/114) and the positive expression of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It appeared to be related with lymph node metastasis of breast cancer (p=0.02) and correlation analysis indicated that legumain expression was correlated positively with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05). Positive legumain expression was significantly associated with shorter overall survival time in breast cancer patients (log-rank p<0.01). Multivariate survival analysis suggested that the positive legumain expression was an independent predictor of poorer overall survival in patients with breast cancer (HR=0.24; 95%CI 0.11-0.65, p=0.03). Legumain might be a new potential biomarker for breast cancer, which may reflect the prognosis and overall survival.

Clinical Implications of CSN6 Protein Expression and Correlation with Mutant-type P53 Protein in Breast Cancer

Constitutive photomorphogenesis 9 subunit 6, as one subunit of the constitutive photomorphogenesis 9, plays an important role in tumor development. The aim of the study was to investigate the clinical and prognostic implications of constitutive photomorphogenesis 9 subunit 6 protein in breast cancer. We examined mastectomy specimens from 92 invasive breast cancers and matched with 20 adjacent non-cancerous tissues using immunohistochemistry. The positive expressions of constitutive photomorphogenesis 9 subunit 6 protein in invasive breast cancer and adjacent non-cancerous tissue were 32.61% (30 of 92) and 10% (2 of 20), respectively. The positive expression of constitutive photomorphogenesis 9 subunit 6 protein was related to tumor size, histological type and lymph node metastasis (P = 0.015, 0.009 and 0.009, respectively). After univariate analysis, constitutive photomorphogenesis 9 subunit 6-positive expression was only found to be significantly related to mutant-type P53 expression (P < 0.001). Spearman's correlation analysis was used to demonstrate negative correlations between constitutive photomorphogenesis 9 subunit 6 and mutant-type P53 (r = -0.417). Constitutive photomorphogenesis 9 subunit 6 positive was associated with both poorer breast cancer-specific survival in 92 cases and in the lymph node-positive group (P = 0.007 and 0.024, respectively). In the Cox regression test, constitutive photomorphogenesis 9 subunit 6 protein was not shown to be an independent prognostic factor for breast cancer. Constitutive photomorphogenesis 9 subunit 6 might be a new potential biomarker for breast cancer. However, the underlying mechanisms of constitutive photomorphogenesis 9 subunit 6's involvement are still unclear.

The Discrepancy Between Genetic Polymorphism of p53 Codon 72 and the Expression of p53 Protein in Helicobacter pylori-Associated Gastric Cancer in Korea

The p53 gene has been referred to as 'the guardian of the genome' because it controls apoptosis and cell cycle arrest. The purpose of this study was to evaluate the association of p53 codon 72 genetic polymorphism and the p53 immunohistochemistry with Helicobacter pylori-associated gastroduodenal diseases, including gastric cancer. This study included 1,852 subjects: controls and patients with gastric cancer, dysplasia, benign gastric ulcers, and duodenal ulcers (DU). Biallelic polymorphism was genotyped by restriction fragment length polymorphism. Immunohistochemical analysis for the detection of mutant type p53 expression was performed. The frequency of the Pro/Pro allele of the p53 codon 72 was higher in the patients with H. pylori-positive dysplasia than in controls (OR: 2.3, 95% CI: 1.3-4.3), but it was less frequent among patients with a H. pylori-positive DU (OR: 0.5, 95% CI: 0.3-0.8). However, there was no significant association with gastric cancer, including the location, stage, or histological type of gastric cancer. Expression of a mutant type of p53 protein was detected in 6.3% of dysplastic tissues and 26.5% of cancerous tissues compared 0% in the controls. Positive expression was higher in the intestinal type of cancer (34.9%) than in the diffuse type (15.0%; P = 0.001). These results suggest that genetic polymorphism of p53 codon 72 played a role in the determination of H. pylori-associated gastroduodenal diseases, but p53 immunostaining did not correlate with those of the p53 genetic polymorphism analysis.

Unventilated Indoor Coal-Fired Stoves in Guizhou Province, China: Cellular and Genetic Damage in Villagers Exposed to Arsenic in Food and Air

BackgroundInorganic arsenic (iAs) is a well-known human carcinogen recognized by the World Health Organization and the International Agency for Research on Cancer. Currently, most iAs studies in populations are concerned with drinking water and occupational arsenicosis. In Guizhou province, arsenicosis caused by the burning of coal in unventilated indoor stoves is an unusual type of exposure. Because the poisoning mechanism involved in arsenicosis is as yet unknown and no effective therapy exists, progress has been slow on the prevention and therapy of arsenicosis.ObjectivesWe examined the relationship between arsenic (As) exposure from the burning of coal in unventilated indoor stoves and genetic damage in humans, using cellular and molecular indices. We selected villagers from Jiaole township, Guizhou province, China, who had been exposed to milligram levels of As daily via food and air contaminated by the burning of As-containing coal in unventilated indoor stoves.ResultsThe As-exposed subjects from Jiaole were divided into four groups according to skin lesion symptoms: nonpatients, mild, intermediate, and severe arsenicosis. Another 53 villagers from a town 12 km from Jiaole were recruited as the external control group. In the four groups of exposed subjects, As concentrations in urine and hair were 76–145 μg/L and 5.4–7.9 μg/g, respectively. These values were higher than those in the external control group, which had As concentrations of 46 μg/L for urine and 1.6 μg/g for hair. We measured sister chromatid exchange and chromosomal aberrations to determine human chromosome damage, and for DNA damage, we measured DNA single-strand breaks and DNA–protein cross-links. All measurements were higher in the four exposed groups compared with the external control group. DNA repair was impaired by As exposure, as indicated by the mRNA of O-6-methylguanine-DNA methyltransferase (MGMT), X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), and, to a lesser extent, by the mismatch repair gene hMSH2 mRNA. The expression of mutant-type p53 increased with aggravation of arsenicosis symptoms, whereas the expression of p16-INK4(p16) decreased. p53 mutated at a frequency of 30–17% in the carcinoma (n = 10) and precarcinoma (n = 12) groups. No mutation was found in p16, although deletion was evident. Deletion rates were 8.7% (n = 23) and 38.9% (n = 18) in noncarcinoma and carcinoma groups, respectively.ConclusionsThe results showed that long-term As exposure may be associated with damage of chromosomes and DNA, gene mutations, gene deletions, and alterations of DNA synthesis and repair ability.

Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model

To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model. VX2 tumor was grown in the liver of 24 rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only, group B receiving combined Ad-p53 therapy and trans-arterial embolization (lipiodol), group C receiving trans-arterial chemoembolization (lipiodol + mitomycin C), control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13). Interventional procedure was applied (d 14). Tumor volume (V2) was assessed by MRI (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI, specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody. The positive expression was scored. Compared with control group (chi= 3.14 +/- 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P<0.05). A slight difference was found between group A (chi = 2.35 +/- 0.59) and group B (chi = 1.75 +/- 0.28) (P=0.048). No statistically significant difference was observed between group B and group C (chi = 2.00 +/- 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P<0.05). Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them. Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.

Maspin expression in early oral tongue cancer and its relation to expression of mutant-type p53 and vascular endothelial growth factor (VEGF)

Even though oral tongue cancer is generally diagnosed at an early stage, the prognosis is poor due to frequent recurrence. Therefore, it is important to identify factors predictive of recurrence and to treat aggressively those patients with a high probability of recurrence. The relationship between angiogenesis and recurrence in tongue cancer has been widely investigated but no consensus has been reached. Mutant-type p53 and VEGF are known to be related to angiogenesis, and maspin is a potent angiogenic inhibitor but its role in tongue cancer has scarcely been examined. We observed the expression of maspin, mutant-type p53 and VEGF by immunohistochemistry in 33 patients with stages I and II oral tongue cancer. And the relationships between maspin, mutant-type p53, VEGF expression and recurrence were analyzed. Maspin and VEGF displayed a cytoplasmic staining pattern and mutant-type p53 a nuclear pattern. None of expression of maspin, mutant-type p53, and VEGF was significantly correlated with tumor recurrence (p=0.34, 0.56, and 0.33, respectively) and survival. Maspin expression was negatively correlated with both mutant-type p53 expression (p=0.02), and VEGF expression (p=0.01). There was no correlation between age, sex, clinical staging, and recurrence. In conclusion, the expression of maspin is not related to recurrence of early stage oral tongue cancer. It is inversely correlated with that of mutant-type p53 and of VEGF, suggesting that the maspin gene is a mutant-type p53 target in vivo and may contribute to regulate VEGF expression.

Loss of maspin is a helpful prognosticator in colorectal cancer: a tissue microarray analysis

Mammary serpin (Maspin) belongs to the serine protease inhibitor (serpin) superfamily and has been identified as a tumor suppressor. In addition, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. The role of maspin in the tumorigenesis and progression of colorectal cancer is still unclear. Therefore, the first aim of the present study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of patients with colorectal carcinoma undergoing left- or right-sided colectomy. Secondly, maspin expression was correlated with p53 protein expression to gain additional information about a possible regulatory influence of the wild-type p53 protein on maspin; it was also correlated with further patient and tumor characteristics (age, sex, TNM, disease stage, tumor localization, and grading). An immunohistochemical study was performed on 280 carcinoma specimens using the tissue microarray technique. In addition, 80 colorectal adenomas and 60 tumor-free tissues were investigated. Maspin protein expression was detectable in 88–100% of the adenomas and non-tumorous tissues and in 193 out of 280 carcinoma patients (69%; maspin-positive). After a median follow-up of 102 months (23–140 months), the median recurrence-free survival was 80 months for maspin-positive cases (M+) and 42 months for maspin-negative cases (M−) ( p=0.02). The median long-term survival was 98 months for M+ and 57 months for M− ( p=0.03). After 5 years, M+ and M− patients had a total survival of 69% and 38%, and, after 10 years, 45% and 9%, respectively. Mutant type p53 expression was detectable in 178 colorectal carcinomas (64%). Mt p53 was positive in 91 out of 193 M+ (47%) compared with 87 of 87 M− (100%, p<0.001). This study showed that loss of maspin protein correlates with p53 protein activity, with a higher likelihood for the development of tumor relapse, and with a decreased recurrence-free and overall survival in colorectal carcinomas. The determination of the immunohistochemical expression status of maspin might be a helpful independent prognosticator and an applicable tool for the development of therapeutic strategies for patients with this disease.

Maspin in thyroid cancer: its relationship with p53 and clinical outcome

The serine protease inhibitor maspin has been reported to inhibit invasiveness and motility of tumor cells. Additionally, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. In a pre-study we were able to detect maspin protein in papillary thyroid carcinomas (PTC), whereas normal (tumor-free) thyroid tissue, follicular adenomas, follicular carcinomas, poorly differentiated carcinomas and undifferentiated carcinomas of the thyroid were maspin-negative. The first aim of our study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of PTC patients undergoing radical thyroidectomy and postoperative irradiation. Secondly, maspin expression was correlated to p53 protein expression in order to gain additional information on a possible regulatory influence of the wild-type p53 protein on maspin. An immunohistochemical approach study was performed on 68 tumor specimens. Maspin protein expression was detectable in 48 of 68 patients (71%; M+). After a median follow-up of 81 (26-117) months the median recurrence-free survival was 60 (28-117) months for M+ and 42 (11-108) months for M- (p=0.03). After 110 months 83% of patients had recurrence-free disease in M+, whereas in M- only 40% of patients were recurrence-free. The median long-term survival was 81 (42-108) months for M+ and 55 (21-99) months for M- (p=0.03). After 5 years, M+ and M- patients had a total survival of 98 and 80%, and after 9 years 90 and 60%, respectively. Mutant-type p53 expression was detectable in 17 of 68 PTC (25%). Mt p53 was positive in 1 of 47 M+ (2%) compared with 16 of 20 M- (80%, p<0.01). This study indicates that maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing local invasiveness and further systemic progression of papillary thyroid carcinomas. Our data hint of a p53-dependent regulatory pathway of the maspin protein in human cancer.

Changes of mutant-type p53 expression in squamous cell carcinoma of the head and neck during radiation therapy and its clinical significance: comparison of an immunohistochemical method and PCR-SSCP assay.

P53 has been reported to be one of tumor suppressor genes that play a major role in signal transduction following many kinds of stresses, including ionizing radiation. Changes in p53 expression during radiation therapy in tumor tissues have not yet been reported. We determined whether radiotherapy changes p53 expression in human squamous cell carcinomas of the head and neck, and established the possible correlations between p53 expression and the therapeutic effects of radiation therapy. 30 patients with tumors of the oral cavity, oropharynx, and maxillary sinus were examined, and all the tumors were confirmed as squamous cell carcinomas. Biopsies were performed on the cancer tissues before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and the specimens were preserved in liquid nitrogen for further examination. Samples were immunohistochemically stained using streptoavidin-biotin peroxidase method and a monoclonal antibody against p53 (Ab-3, mutant type). For all the samples p53 PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) assays were performed. 14 of the 30 patients with squamous cell carcinomas showed expression of p53 in their tumor cells before and/or at 4 Gy or 10 Gy of radiotherapy. Eleven of the 14 tumors showed high radiosensitivity. Results of the p53 PCR-SSCP assays revealed mutations of p53 in 13 of 30 patients examined, and percentages of mutated p53 DNA varied at radiation doses of 4 Gy and 10 Gy. Ten of 12 patients with mutated p53 in their tumors showed decreased percentages of mutated p53 DNA during radiotherapy. The relationship between the immunohistochemical findings and the antitumor effect of a radiation dose of 20 Gy was examined on the correspondent hematoxylin-eosin sections. In patients whose p53 expressions in tumor cells were grades + or ++ or before radiotherapy and/or at 4 Gy of radiotherapy, the tumors responded significantly well to radiation therapy but the patients responded with significantly unfavorable clinical courses. The high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of mutant type p53 in the tumor cells, and these mutant type p53-positive tumor cells possibly showed radioresponsiveness.

Ki-ras point mutation in codon 12 and expression ofp53 in mucin-producing tumor of the pancreas

Mucin-producing tumors (MPTs) of the pancreas show a variety of clinical characteristics, including massive production of mucin in the pancreatic duct, dilatation of the main pancreatic duct, and a better prognosis than common invasive ductal carcinoma (IDC). These characteristics suggest that MPTs and IDCs have different cytomolecular backgrounds. The present study was designed to assess the differences in cytomolecular background between MPTs and IDCs, especially the differences in Ki-ras point mutation (PM) and wild and mutant typep53 expression. Cytomolecular backgrounds were compared in a 13 MPTs [8 carcinomas (MPCas) and 5 benign tumors (MPBTs)] and 36 IDCs. Cytomolecular studies included the evaluation of Ki-ras PM and the expression of Ki-ras p21, wild-typep53 (w-p53), and mutant-typep53 (m-p53). Ki-ras PM was assessed by the allele-specific oligonucleotide dot blot hybridization method, and the expression of p21 andp53 was assessed by an immunohistochemical staining method with monoclonal antibodies. Ki-ras PM was seen in 97% of IDCs and in 77% of MPTs (100% of MPCas and 40% of MPBTs), and MPBTs showed a significantly lower incidence of Ki-ras PM (versus IDC,P < 0.01). Guanine-Guanine-Thymine (GGT) to Guanine-Adenine-Thymine (GAT) mutation was seen in 55% of IDCs and 62% MPTs (87% of MPCas and 20% of MPBTs), and MPCas showed a significantly higher incidence of percent GAT mutation (versus IDC,P < 0.05). Ki-ras p21 was expressed in 43% of IDCs and in 31 % of MPTs (50% of MPCas and 20% of MPBTs). w-p53 and m-p53 were expressed in 51 % and 78% of IDCs and in 54% and 62% of MPTs (38% and 63% of MPCas and 20% and 60% of MPBTs), respectively. In MPBTs, hyperplasias showed higher rates of p21, w-p53, and m-p53 expression than cystadenomas. The study suggested that GAT mutation may be involved in the tumorigenesis of MPTs. It is suggested that MPBTs, especially hyperplasias, may be classified as low-grade malignancies like MPCas.