[Correlation between tumor cell proliferation and prognosis of primary cutaneous malignant melanoma in 127 patients].

OBJECTIVE: To investigate the correlations among Ki-67 expression, mitosis and other clinicopathological parameters of primary cutaneous malignant melanoma, and search for prognostic factors of malignant melanoma. METHODS: Totally 127 cases of primary cutaneous malignant melanoma were collected from Beijing Cancer Hospital. Immunohistochemical study for Ki-67 was performed, and the mitosis was calculated referring to "hot spot" method recommended by the seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system. The correlations of Ki-67 expression, mitosis and other clinicopathological parameters were analyzed, and the survival analysis of all these risk factors including TNM and Clark level was conducted based on follow up data. RESULTS: The expression level of Ki-67 was associated with necrosis and Breslow thickness (P < 0.05). Mitosis was correlated with Clark level and Ki-67 expression (P < 0.05). Univariate analysis indicated Ki-67 expression level (P = 0.043), mitosis (P = 0.030) and TNM stage (P < 0.001) might influence the survival of patients. However, multivariate analysis showed that the TNM staging was the only independent prognostic factor affecting survival. CONCLUSIONS: The prognosis of patients with primary cutaneous malignant melanoma was closely related to the TNM staging at the fist examination. Ki-67 expression and mitosis are two important clinicopathological parameters of primary cutaneous malignant melanoma.

[Expression and prognostic significance of galectin-1 and galectin-3 in benign nevi and melanomas].

OBJECTIVE: To study the expression and prognostic significance of galectin-1 and galectin-3 in different melanocytic lesions. METHODS: The expression of galectin-1 and galectin-3 in 39 cases of benign nevus, 58 cases of primary cutaneous melanoma, 24 cases of primary mucosal melanoma, 69 cases of melanoma with lymph node metastasis and 8 cases of melanoma with distant metastasis were studied by immunohistochemistry and tissue microarray. RESULTS: The expression of galectin-1 and galectin-3 was higher in benign nevi than in melanomas (P < 0.01). The nuclear expression of galectin-3 was higher in primary cutaneous melanomas than in primary mucosal melanomas or melanomas with metastases (P < 0.01, respectively). The expression correlated with age of patients (P < 0.05), necrosis (P < 0.05) and survival time (P < 0.01). Clark's level also correlated with survival time in patients with cutaneous melanomas (P = 0.037). TNM staging was the only independent prognostic factor for melanomas (P < 0.01). CONCLUSIONS: The expression of galectin-1 and galectin-3 is decreased in melanomas. The decrease in nuclear expression of galectin-3 may represent a poor prognostic factor for melanomas. TNM staging is an independent prognostic factor which influences the survival time.

Correlation of diffusion-weighted imaging data with apoptotic and proliferation indexes in CT26 colorectal tumor homografts in balb/c mouse.

PURPOSE: To investigate whether the percentage of apparent diffusion coefficient (ADC) changes could be used as an imaging marker related to tumor cell apoptotic and Ki-67 proliferation index of tumors. MATERIALS AND METHODS: Mice bearing CT26 colorectal carcinoma tumors were scanned before radiotherapy, then divided into radiotherapy (n = 24) and control groups (n = 24). Diffusion-weighted imaging (DWI) and anatomic T2WI were performed on six randomly chosen mice in total from two groups at different timepoints after radiotherapy (4, 8, 12 hours, 1, 2, 3, 5, 7 days). After imaging, six animals were sacrificed at each timepoint and histological analyses were undertaken. ADC maps were calculated on a pixel-by-pixel basis using built-in software (Functool, GE). Regions of interest were manually circumscribed for all high-signal areas on lesions observed during DWI. The percentage of ADC changes were calculated at predefined timepoints and compared with the apoptotic and proliferation index from the histological analyses by using the Pearson correlation test. RESULTS: A significant positive correlation was found between the percentage of ADC changes of the viable tissue and apoptotic index. A significant negative correlation was found between the percentage of ADC changes of the viable tissue and Ki-67 proliferation index. CONCLUSION: Our results suggest that the percentage of ADC changes can be used as a measurement of cell apoptotic and proliferation index in colorectal carcinoma.

[Epidermal growth factor receptor gene mutations and clinicopathologic correlation in 309 patients with non-small cell lung cancer].

OBJECTIVE: To investigate the epidermal growth factor receptor (EGFR) gene mutation profile and related clinicopathological features in Chinese patients with non-small cell lung carcinoma (NSCLC). METHODS: Optimized oligonucleotide probe method was applied to detect EGFR mutations involving exons 18 - 21 using formalin fixed paraffin embedded tissue specimens of 309 NSCLC patients. The relationship between EGFR mutations and clinicopathological features were analyzed. RESULTS: The overall EGFR mutation rate was 34% (105/309) in this study cohort. Mutation rates in male and female were 30.4% (56/184) and 39.2% (49/125), respectively. The mutation rate was higher in patients less than 60 years of age, non-smokers and adenocarcinoma subtype than in their counterparts (P<0.05), with the percentage of 40.5% (87/215), 40.2% (51/127), 38.8% (78/201), respectively. The EGFR mutation types included exon 18 G719X mutation (5.7%, 6/105), exon 19 deletion (39.0%, 41/105) and exon 21 L858R mutation (55.2%, 58/105). In large cell undifferentiated carcinomas and squamous cell carcinomas, EGFR mutation rates were 22.2% (58/105) and 3/14, respectively. The overall mutation rate of exon 18 was low, but the proportion of its mutation was higher in squamous and adenosquamous carcinomas than in adenocarcinomas. CONCLUSIONS: There is a higher EGFR mutation rate in female, age of less than 60 years, non-smoker and adenocarcinoma among Chinese patients with NSCLC. Optimized oligonucleotide probe method is a sensitive and convenient method for the detection of EGFR mutations.

[Comparison of pathologic and clinical characteristics of young and old patients with advanced rectal cancer after neoadjuvant radiotherapy].

OBJECTIVES: To address the difference of pathologic and clinical characteristics of the young and the middle-aged and elderly patients with advanced rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 252 patients undergoing radical surgery from January 2000 to January 2005 were included in this study. The patients were divided into two groups according to the age at diagnosis:young-patient group (< 40 years) and old-patient group (≥ 40 years). The pathologic and clinical materials were collected and the oncologic outcome was compared between the two arms. RESULTS: A total of 252 patients were included in this study, included 54 patients in young-patient group and 198 patients in old-patient group, respectively. There was no significant difference in gender, clinical stage and pretreatment serum carcinoembryonic antigen (CEA) between the two groups. However, the proportion of mucinous and signet-ring cell cancer was significantly higher in young-patient group (20.4% vs. 4.0%, P < 0.05), and furthermore, the proportion of pathologic stage later than IIIA was also significantly higher in the young-patient group (61.1% vs. 42.9%, P < 0.05). There was no significant difference in local recurrence rate between the patients who received neoadjuvant radiotherapy and those who did not in the young-patient group, whereas the difference was observed significant in the old-patient group (3.3% vs. 11.2%, P < 0.05). There was no significant difference in both the disease free survival and overall survival between the two arms (5y-DFS: 63.3% vs. 68.5%, P > 0.05; 5y-OS: 73.5% vs. 72.9%, P > 0.05). CONCLUSIONS: Rectal cancer in young patients has poorer histologic differentiation and more advanced pathologic stage, but the long-term survival is similar to that in middle-aged and elderly patients. The local control effect of neoadjuvant radiotherapy on rectal cancer in young patients still need to be further investigated.

Detection of mosaic pattern of mitochondrial DNA alterations in different populations of cells from the same endometrial tumor.

Somatic mitochondrial DNA (mtDNA) alterations including point mutations and microsatellite instability (MSI) have been frequently detected in human cancers. To further explore the extensiveness of mtDNA alterations, we have analyzed the occurrence of somatic mtDNA mutations in different populations of endometrial cancer cells from the same tumor tissues as compared with adjacent non-tumor cells. Laser-captured micro-dissection was used to harvest endometrial cancer cells from separated areas of the same tumor and adjacent normal cells. Total DNA isolated from micro-dissected cells was PCR amplified and analyzed for mtDNA alterations by polyacrylamide gel electrophoresis and DNA sequencing. Multiple mtDNA alterations were detected in different portions of the same tumor. Different populations of endometrial cancer cells carried different patterns of mtDNA mutations. Interestingly, unlike previous reports, most mutations were found to be heteroplasmic. We have demonstrated the occurrence of hyper-variability of mtDNA alterations in a single piece of tumor tissue. Our observations support the hypothesis that the accumulation of mtDNA alterations is random and expands independently. The data presented here showed the heterogeneity of cancer cells in terms of mtDNA alterations in endometrial cancer.

[Clinicopathologic analysis and expression of cyclin D1 and p53 of ovarian borderline tumors and carcinomas].

OBJECTIVE: To study the clinicopathological features and expression of cyclin D1 and p53 in epithelial ovarian tumors, and to investigate the correlation between pathogenesis of ovarian cancer and epithelial borderline tumors. METHODS: Fifty four cases of ovarian borderline tumors and 45 cases of ovarian carcinomas from the People's Hospital, Peking University were reviewed retrospectively. The clinical data and pathological findings were analyzed. Immunohistochemical study of cyclin D1 and p53 was performed in all 99 cases. RESULTS: (1) In borderline tumors, the age of patients ranged from 14 - 82 (mean age = 42.5) years. International Federation of Gynecology and Obstetrics (FIGO) stage of borderline tumors was stage I in 48 cases, stage II in 3 cases, and stage III in 3 cases. In ovarian carcinomas, the age of patients ranged from 26 - 80 (mean age = 53.5) years. FIGO stage of carcinoma was stage I in 6 cases, stage II in 8 cases, stage III in 26 cases, and stage IV in 5 cases. In follow-up of 54 cases with borderline tumors the 5-year survival rate was 98% and of 45 cases with carcinomas a 5-year survival rate of 51% was noted. (2) In 54 cases of borderline tumors, mucinous types accounted for 56% (30/54) and serous types accounted for 30% (16/54). There were 5 cases with micropapillary pattern, 3 cases with peritoneal implants, 3 cases with lymph node involvement, 6 cases with microinvasion, one case with intraepithelial carcinoma, and one case with mural nodules. In 45 cases of carcinomas, serous carcinoma was the most (49%, 22/45). The remainder included 3 cases of mucinous types, 8 cases of endometrioid types, 6 cases of transitional cell types, 3 cases of mixed phenotype and 3 cases of undifferentiated types. (3) Overexpression of cyclin D1 and p53 was observed in 31% (14/45) and 56% (25/45) of ovarian carcinomas, respectively. There was a significant association between p53 overexpression and tumor grade. In the borderline tumor group, 69% (37/54) had overexpression of cyclin D1 and 6% (3/54) had overexpression of p53. There were significant differences in expression of cyclin D1 and p53 between conventional serous borderline tumors and high-grade serous carcinomas (cyclin D1: 91% vs 26%; p53: 0 vs 58%). However, micropapillary serous borderline tumors and low-grade serous carcinomas showed remarkably similar expression of cyclin D1 and p53. CONCLUSIONS: Epithelial ovarian borderline tumors are distinct from ovarian cancer in clinical progress and prognosis, and histological types. Overexpression of cyclin D1 is common in ovarian borderline tumors and low grade carcinomas. And overexpression of p53 is more common in high grade ovarian carcinomas. Conventional serous borderline tumors are distinct from high-grade serous carcinomas in pathogenesis. Micropapillary serous borderline ovarian tumors may be closely related to low grade serous carcinomas.

Single nucleotide polymorphism of pi-class glutathione s-transferase and susceptibility to endometrial carcinoma.

PURPOSE: Endometrial carcinoma is the most common gynecologic cancer in developed countries. Prolonged unopposed estrogen exposure has been identified as the major risk factor. The pi-class glutathione S-transferase (GSTP1) is a phase II metabolic enzyme that is important in the detoxification of a wide range of electrophiles including carcinogenic steroid-hormone intermediates generated through oxidative metabolism. In this study, we aimed at determining the association between the GSTP1 polymorphism and the risk of endometrial carcinoma in a Chinese population. EXPERIMENTAL DESIGN: Genotyping of 180 cases and 200 age-matched controls were assessed by PCR-RFLP approach and confirmed by direct sequencing. RESULTS: Statistical analysis showed that patients of valine allele carriers had 2.03-fold of increased risk of developing endometrial carcinoma (P < 0.01). The allele frequencies for the Ile and Val variants between the cancer cases and controls were also significantly different (P < 0.01; odds ratio, 1.59; 95% confidence interval, 1.13-2.23). Such association was shown in endometrial cancers as a group and in type I endometrioid adenocarcinoma but not the type II nonendometrioid adenocarcinoma. In addition, the Val allele was found significantly associated with high-grade endometrial cancer and/or endometrial cancer of deep myometrial invasion (P < 0.01). Interestingly, the relatively low frequency of Val/Val genotype in both the cancer cases and controls, in parallel with the lower incidence of endometrial cancer in Chinese, was observed when compared with those in Caucasians. CONCLUSIONS: Our findings suggested that the GSTP1 Ile(105)Val polymorphism was associated with an increased risk of endometrial cancer. Further studies may be required to explore the possible significance of these polymorphisms on GSTP1-related metabolism that may affect the susceptibility of Asians to endometrial carcinoma.

Promoter methylation and differential expression of pi-class glutathione S-transferase in endometrial carcinoma.

Pi-class glutathione S-transferase (GSTP1), located on chromosome 11q13, codes for a phase II metabolic enzyme that detoxifies reactive electrophilic intermediates. The protein also interacts with steroid hormones in the human body. The role of GSTP1 in endometrial carcinoma has not been reported. In this study, we aimed at determining the expression of GSTP1 in relation to the epigenetic and genetic changes of the gene in endometrial carcinoma. The GSTP1 protein and mRNA expression was assessed by immunohistochemistry on tissue microarray and quantitative real-time reverse transcriptase-polymerase chain reaction, respectively. Its methylation status was studied by methylation-specific polymerase chain reaction and bisulfite sequencing. Possible mutations in coding region of GSTP1 were assessed by cDNA sequencing. Ninety-seven cases of endometrial carcinoma with available tissue blocks and clinical data were studied. Our results showed that 68.0% (66 of 97) of the cases showed reduced protein expression while 64% (16 of 25) showed reduced mRNA expression; 30.9% (30 of 97) of the cases demonstrated methylated alleles in at least one of the six methylation-specific polymerase chain reaction reactions. The methylation status significantly correlated with reduced protein expression (P = 0.008) and reduced mRNA expression (P = 0.003). Methylation at non-CpG sites including CpCpG trinucleotides and CpT dinucleotides were also observed. cDNA sequencing did not reveal genetic alterations in coding region of the gene. The extent of myometrial invasion was found to be significantly correlated with both the methylation status (P = 0.009) and the protein expression (P = 0.036) of the GSTP1 gene. We postulated that hypermethylation of the GSTP1 gene promoter region may act as a dynamic regulation mechanism contributing to reduced GSTP1 expression, which is associated with myometrial invasion potential of the endometrial carcinoma.

Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver.

AIM: The expression pattern of endoglin (CD105) in hepatocellular carcinoma (HCC) has not been reported so far. We hypothesized that CD105 could differentially highlight a subset of microvessels in HCC, and intratumoral microvessel density (IMVD) by CD105 immunostaining (IMVD-CD105) could provide better prognostic information than IMVD by CD34 immunostaining (IMVD-CD34). METHODS: Paraffin blocks of tumor and adjacent non-tumorous liver tissues from 86 patients who underwent curative resection of HCC were used for this study. Serial sections were stained for CD105 and CD34, respectively, to highlight the microvessels. IMVD was counted according to a standard protocol. RESULTS: In the HCC tissues, CD105 was either negatively or positively stained only in a subset of microvessels. In contrast, CD34 showed positive and more extensive microvessel staining in all cases examined. However, in the adjacent non-tumorous liver sections, CD105 showed a diffuse pattern of microvessel staining in 20 of 86 cases, while CD34 showed negative or only focal staining of the sinusoids around portal area. Correlation with clinicopathological data demonstrated that lower scores of IMVD-CD105 were found in larger sized tumors (mean 41.4/0.74 mm2 (>5 cm tumor) vs 65.9/0.74 mm2 (< or =5 cm tumor), P = 0.043) and more aggressive tumors, as indicated by venous infiltration (36.8/0.74 mm2 (present) vs 64.2/0.74 mm2 (absent), P = 0.020), microsatellite nodules (35.1/0.74 mm2 (present) vs 65.9/0.74 mm2 (absent), P = 0.012), and advanced TNM tumor stage (38.8/0.74 mm2 (stage 3 or 4) vs 68.3/0.74 mm2 (stage 1 or 2), P = 0.014). No prognostic significance was observed when median values were used as cut-off points using either IMVD-CD105 or IMVD-CD34. However, the presence of the diffuse pattern of CD105 expression in the adjacent non-tumorous liver tissues predicted a poorer disease-free survival (median 8.6 vs 21.5 mo, P = 0.026). CONCLUSION: Our data demonstrate that a lower IMVD-CD105 is associated with larger and more aggressive tumors. In this study, IMVD-CD105 did not provide significant prognostic information. However, active angiogenesis as highlighted by diffuse CD105 staining of the microvessels in the adjacent non-tumorous liver tissues is predictive of early recurrence.

Promoter hypermethylation of multiple genes in hydatidiform mole and choriocarcinoma.

The methylation status of genes in hydatidiform mole and choriocarcinoma and its significance is relatively unexplored. We investigated the methylation status of the promoter regions of six genes, p16, HIC-1, TIMP3, GSTP1, death-associated protein kinase (DAPK), and E-cadherin in 54 hydatidiform moles, five choriocarcinomas, and 10 first trimester placenta by methylation-specific polymerase chain reaction (PCR). Immunohistochemical expression of p16, TIMP3, and E-cadherin, and quantitative real-time RT-PCR of p16 was also performed. Among the six genes examined, the promoter region of four genes (E-cadherin, HIC-1, p16, TIMP3) in choriocarcinoma and three genes (E-cadherin, HIC-1, p16) in hydatidiform mole exhibited aberrant methylation whereas none was hypermethylated in normal placenta. There was a significant correlation between methylation and reduced expression of p16, E-cadherin, and TIMP3 (P < 0.001). Fifteen of the 54 patients with hydatidiform mole developed gestational trophoblastic neoplasia requiring chemotherapy. Promoter hypermethylation of p16 alone, or combined with E-cadherin, was significantly correlated to such development (P = 0.001, 0.0005, respectively). Hypermethylation of multiple genes, especially p16, might be related to the subsequent development of gestational trophoblastic neoplasia.

Cervical and peritoneal fluid cytology of uterine sarcomas.

OBJECTIVE: To study the cytologic features of uterine sarcoma. STUDY DESIGN: The pathology records of 102 patients with uterine sarcoma were reviewed. Four patients, including one case of leiomyosarcoma (LMS), one high grade stromal sarcoma (HGSS) and two malignant mixed müllerian tumor (MMMT), had abnormal cervical and/or peritoneal cytologic findings. Three abnormal cervical smears and two abnormal peritoneal fluids from these patients, including immunohistochemically stained sections of cell block, were reviewed. RESULTS: The diagnostic cells appeared in clusters or in isolation. They had enlarged and hyperchromatic nuclei. Occasional mitotic figures were seen. The cells were considered suspicious for malignancy in cervical smears of HGSS and in the peritoneal fluid of LMS. Adenocarcinoma cells were identified in both the cervical smear and peritoneal fluid of one patient with MMMT. Atypical cells were found in another patient with MMMT. CONCLUSION: Positive cervical or peritoneal cytology is uncommonly detected in association with uterine sarcomas. Even when abnormal cells are found, it may be difficult to give a definitive diagnosis of uterine sarcoma based directly on the cytomorphologic characteristics of cervical or peritoneal smears. However, such a possibility should be kept in mind by the cytopathologist to avoid missing the diagnosis.

Endometrial stromal sarcoma of uterus.

Endometrial stromal sarcomas are the second most common uterine sarcomas. Currently, they are classified into low-grade endometrial stromal sarcomas and undifferentiated endometrial sarcoma. Low-grade endometrial stromal sarcomas are biologically low-grade uterine sarcomas, and typically composed of uniform cells intimately associated with prominent arterioles, resembling the endometrial stroma in proliferative phase. There is usually little cytological atypia or pleomorphism, and mitoses are scanty. In contrast, undifferentiated endometrial sarcomas are frankly malignant, lack specific differentiation and any features of normal endometrial stroma. It is a highly aggressive neoplasm, often exhibiting myometrial invasion, haemorrhage and necrosis, as well as marked nuclear pleomorphism and high mitotic activity. The diagnosis of undifferentiated endometrial sarcoma is reached after excluding other uterine tumours with a sarcomatous component, such as adenosarcoma and malignant mixed Müllerian tumour. Histological variants of endometrial stromal sarcomas, including the so called 'high-grade endometrial stroma sarcomas' are addressed. The problems with histologic diagnosis and application of immunohistochemical studies and molecular pathology are highlighted.

Oncologic outcomes of primary and post-irradiated early stage rectal cancer: a retrospective cohort study.

AIM: To evaluate the oncologic outcomes of primary and post-irradiated early stage rectal cancer and the effectiveness of adjuvant chemotherapy for rectal cancer patients. METHODS: Eighty-four patients with stage I rectal cancer after radical surgery were studied retrospectively and divided into ypstage I group (n = 45) and pstage I group (n = 39), according to their preoperative radiation, and compared by univariate and multivariate analysis. RESULTS: The median follow-up time of patients was 70 mo. No significant difference was observed in disease progression between the two groups. The 5-year disease-free survival rate was 84.4% and 92.3%, respectively (P = 0.327) and the 5-year overall survival rate was 88.9% and 92.3%, respectively, for the two groups (P = 0.692). The disease progression was not significantly associated with the pretreatment clinical stage in ypstage I group. The 5-year disease progression rate was 10.5% and 19.2%, respectively, for the patients who received adjuvant chemotherapy and for those who rejected chemotherapy in the ypstage I group (P = 0.681). CONCLUSION: The oncologic outcomes of primary and post-irradiated early stage rectal cancer are similar. Patients with ypstage I rectal cancer may slightly benefit from adjuvant chemotherapy.

Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy.

AIM: To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. METHODS: Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resectable locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. RESULTS: The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). CONCLUSION: MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.

[Clinicopathological observation of gastric cancer with pathological complete response following neoadjuvant chemotherapy].

OBJECTIVE: To observe the clinicopathological characteristics of gastric cancer with pathological complete response(pCR) following neoadjuvant chemotherapy. METHODS: Data of gastric cancer patients who received neoadjuvant chemotherapy from 2002 to 2008 in the Beijing Cancer Hospital were reviewed. Five cases were found to have pCR. The slides were reviewed by two experienced pathologists independently. Histological structure, morphology of tumor cells, morphology and quantity of stromal cells were evaluated. RESULTS: Structure of the gastric wall was distinguishable in all the 5 cases, while distortion and rupture of muscular layer were found in 2 cases. Exudative inflammatory reaction was present in the whole gastric wall including the serosa layer. Three patients had ulcerative lesions with epithelial layer shedding, and atypical hyperplasia was found around the border of the ulcer, and vascular endothelial cells were swollen. Residual distorted necrotic tumor cells resided in 1 case only and no residual tumor cells was present in the other 4 patients. Significant hyperplasia of fibroblasts was present in 4 cases, large amount of lymphocytes infiltration in 3 cases including concurrent plasma cell infiltration in 1 case, multinucleated giant cell reaction in the muscular layer of 1 case, and foam cells aggregation in 1 case with mucinous adenocarcinoma. In addition, there were 2 cases with pCR had lymph node metastasis. CONCLUSIONS: For cases with pCR following neoadjuvant chemotherapy, heterogeneity of stromal cells reaction is found in previous tumor site. Furthermore, the response of primary tumor does not necessarily parallel to that of lymph nodes.