Non-mucinous Tumor Research Articles

Correlation of Ki-67 Proliferating Index with Histological Types and Characterization of Mucin in Colorectal Carcinoma

Background: Colorectal carcinoma is a major cause of cancer associated with a high rate of morbidity and mortality in the western world. One of the pathologic features considered to be important for prognosis is mucin production. Many authors confirmed that colon carcinomas with high mucin content tend to recur locally and carry a poor prognosis. Aim: Correlation of Ki-67 proliferating index with different type of colorectal carcinoma as well as characterization of mucin. Method: This cross sectional study was conducted at Sir Salimullah Medical College, Department of pathology from July 2014 to June 2016. Ninety eight patients with colorectal carcinoma was enrolled in this study who underwent surgical resection of colon, adenocarcinomas. For histological classification we used the WHO recommendation (2000) and to be more accurate we sub-classified mucinous adenocarcinomas by morphometrical analysis in three categories: pure mucinous, with extracellular mucin more than 80% of the tumoral volume; mixed type, with 50–80% extracellular mucin; and mixed type with less than 50% extracellular mucin and their correlation with Ki-67 proliferating index . For histochemical investigation, we used stains such as: D- PAS and Alcian Blue. A technique of manual tissue array was employed to see Ki-67 expression by IHC method. Ki-67 is a proliferation associated nuclear antigen which can be recognized by MIB-1 monoclonal antibody. Result: It was observed that Ki-67 labeling index was high in nonmucinous tumor compared to mucinous adenocarcinoma and signet ring cell carcinoma which is statistically significant (P<0.05). Histochemical stain of mucin where both D-PAS and Alcian Blue positive cases(mixed type) are more than the Only D-PAS positive cases(pure type). Ki-67 proliferating index was also high in mixed type mucinous adenocarcinoma (<50%) compared to pure (>80%) and mixed type (50-80%). The result was statistically significant (p<0.05). Correlation of Ki-67 proliferating index with histologic type as well as mucin characterization and thereby provide information to clinician to better understanding of the treatment as well as prognosis.

Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Invasive Papillary Carcinoma of the Breast Presenting after Metastatic Mucinous Adenocarcinoma: Report of a Rare Case

Breast cancer constitutes a heterogenous group of lesions. Invasive papillary carcinoma of the breast is a rare form of breast cancer with less aggressive behavior which may have mucinous differentiation. Histologically papillary projections with fibrovascular core and epithelial proliferation are present. Signet ring morphology and extracellular mucin production can be seen but myoepithelial cells are absent. We reported a case of invasive papillary carcinoma of the breast in a 74-year-old lady without mucin production, which first presentation was a metastasis of unknown origin to the spinal column as adenocarcinoma with mucin production. In conclusion, although invasive papillary carcinoma of the breast is known as a less aggressive tumor, but its presentation may be with metastasis and mucin production, despite of non-mucinous primary tumor.

Immunohistochemical expression of dual-specificity protein phosphatase 4 in patients with colorectal adenocarcinoma.

The role of dual-specificity protein phosphatase 4 (DUSP4) appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P < 0.001). Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P < 0.001). DUSP4 expression was significantly correlated with older age (P = 0.017), male gender (P = 0.036), larger tumor size (P = 0.014), nonmucinous tumor type (P = 0.023), and higher T stage (P = 0.040). Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P = 0.008 and P = 0.003, resp., log-rank test) and male gender (P = 0.017 and P = 0.049, resp., log-rank test). DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis.

Clinicopathologic significance of serum response factor expression in colorectal adenocarcinomas

Background and aim: The purpose of this study was to investigate the role of serum response factor (SRF) expression and to evaluate its correlation with various clinicopathological parameters in colorectal adenocarcinomas. Methods: We used tissue microarrays consisting of 24 normal mucosa, 50 tubular adenomas, 496 adenocarcinomas, and 128 metastatic lesions. Results: The expression of SRF was rare in normal colonic mucosa with a mean expression score of 0.67 ± 0.17. Tubular adenomas had a mean expression score of 2.48 ± 0.31, adenocarcinomas 2.82 ± 0.13 and lymph node metastases 2.82 ± 0.36. Interestingly, SRF expression was high in distant metastases with a mean expression score of 4.83 ± 0.43. The mean SRF expression was increased significantly early in the normal-adenoma-carcinoma sequence and again in distant metastases. The positive SRF expression was strongly correlated with non-mucinous tumor type (P < 0.001). Moderately and poorly differentiated adenocarcinomas had higher mean expression scores than well-differentiated adenocarcinomas (2.88 ± 0.13 vs 1.33 ± 0.32) (P= 0.015). There were significant associations between SRF expression and expression of p53 (P= 0.034) and Ki-67 (P= 0.001). Conclusions: Our results suggest that SRF expression may be the early event of normal-adenoma-carcinoma sequence of colorectal cancer, especially in adenomatous change of colonic mucosa and may play an important role in distant metastasis of colorectal cancers.

Clinicopathologic significance of GLUT1 expression and its correlation with Apaf-1 in colorectal adenocarcinomas

To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. We used tissue microarrays consisting of 26 normal mucosa, 50 adenomas, 515 adenocarcinomas, and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However, GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009), non-mucinous tumor type (P = 0.045), poorer differentiation (P = 0.001), lymph node metastasis (P < 0.001), higher AJCC and Dukes stage (P < 0.001 and P < 0.001, respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis, patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021, respectively, log-rank test). GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.

Expression of Cyclooxygenase-1 and 2 in Epithelial Ovarian Cancer: A Clinicopathologic Study.

BackgroundTo examine the rate and degree of expression of Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) in epithelial ovarian cancer (EOC) and associated with clinicopathological factors and survival.MethodsEOC patients being treated in our institute with available pathological tissue sections during 1996-2003 were identified. Immunohistochemical staining with antibody to COX-1 and COX-2 were studied. Degree of expression was categorized into low and high levels. The degrees of immunohistochemistry staining were associated with clinicopathological factors and overall survival.ResultsA total of 107 patients were included in the study. Most of patients had stage 1 and 3, and the most common histology type was serous carcinoma. The expression rate of COX-1 and COX-2 was 83.2 % and 95.3 %, respectively. Non-mucinous tumor had significant higher level of expression of both COX-1 and COX-2. Except for a high level of expression of COX-2 in association with better response to chemotherapy, no significant association with other clinicopathologic factors were observed. Level of COX-1 or COX-2 expression did not associate with progression-free and overall survival. The combination of COX-1 and COX-2 level was analyzed and the combination of high COX-1 and low COX-2 level significant associated with short progression-free and overall survival.ConclusionEOC in our study showed high rate of COX-1 and COX-2 expression, especially in non-mucinous tumors. High level of COX-2 associated with better response to chemotherapy. Neither COX-1 nor COX-2 expression showed association with survivals while combination of high COX-1 and low COX-2 level of expression was associated with poor progression-free and overall survivals.

Prognosis of Mucinous Adenocarcinoma of the Prostate Treated by Radical Prostatectomy

Mucinous adenocarcinoma of the prostate is one of the least common variants of prostate cancer. The prognosis of this variant of prostate cancer remains controversial. We present 47 cases (1991 to 2006) of mucinous carcinomas treated by radical prostatectomy. Mean patient age at diagnosis was 56 years (range: 44 to 69 y). The mean preoperative prostate-specific antigen (PSA) level was 9.0 ng/mL (range: 1.9 to 34.3 ng/mL). Clinical stages were T1c (34 cases), T2a (7 cases), and T2b (6 cases). The mean percentage of tumor composed of the mucinous component was 52% (range: 25% to 90%). The mean Gleason score was 7 with scores of 6 in 6 cases (12.8%), 7 in 37 cases (78.7%), and 8 in 4 cases (8.5%). Margins were positive in 4 cases of mucinous adenocarcinoma of the prostate. Only 2 cases had isolated margin positivity in the nonmucinous acinar component of cancer. In 12 cases (25.5%), mucinous adenocarcinoma had established extraprostatic extension (EEPE). Eight cases (17.0%) had isolated EEPE of nonmucinous cancer. The 1 lymph node metastasis contained nonmucinous cancer. All together, taking into account both the mucinous and nonmucinous tumor, 20/47 cases (42.5%) had EEPE and 6/47 (12.7%) had positive margins. The 1 lymph node metastasis contained nonmucinous cancer. The mean follow-up for those without progression was 5.6 years (median 6 y, range: 1 to 15 y). One patient (2.1%) progressed 3 years after his radical prostatectomy (5 y actuarial progression-free risk 97.2%). Using the Kattan nomogram, the predicted mean 5-year PSA progression-free risk for nonmucinous prostate cancer with the same PSA and postoperative findings as in the current study was 85.4%. This study confirms that mucinous adenocarcinoma of the prostate treated by radical prostatectomy is not more aggressive, and possibly even less aggressive than nonmucinous prostatic adenocarcinoma.

IFCT0401 trial: Phase II study of gefitinib administered as first line treatment in non-resectable, pneumonic-type adenocarcinoma (P-ADC)

7186 Background: P-ADC is a peripheral lung ADC with a pneumonic radiological presentation, most often containing the bronchioloalveolar carcinoma variant in the 2004 classification. In this setting, EGF receptor tyrosine kinase inhibitors have shown promise. We therefore conducted a prospective multicentric phase II trial to evaluate gefitinib (G) (250 mg/d) as first line treatment in non-resectable P-ADC. Methods: Inclusion criteria: previously untreated, non-resectable cyto/pathologically proven P-ADC with &gt; 3-month expected survival. Primary objective: disease control rate (DCR) - objective response (OR) plus stable disease (SD) for 3 months. Secondary objectives: tolerance, quality-of-life, time-to-progression (TTP), survival, and identification of clinical, pathological and biological markers associated with DC. Results: From 04/04 to 06/05, 88/90 enrolled patients were eligible. All had stage IV disease, with pulmonary (n = 86) and/or extra-thoracic metastasis (n = 10). After review by the clinical trial panel 85/88 were evaluable for response. Tissue-biopsies were collected for central pathological review and molecular analyses. Patients: all Caucasians, median age 64 yrs (27–84), PS &lt;2 in 80.7%, 48 females (54.5%), 33 never (38.6%), 49 former, and 5 current smokers. At 3 months, DC was achieved in 25/85 patients (DCR: 29.4%, CI = [20–39]), including 11 OR (13%, CI = [6–20]) and 14 with SD (16.5% CI = [9–24]). The longest duration of OR is 19.5+ months (4+ to 19.5+) and SD 18+ (5 to 18+). Median TTP is 2.9 months (CI = [2.5–3.3]) but median survival time was not achieved after a 12-month follow-up median time. No death-related toxicity was observed. Only 1 patient stopped G because of skin toxicity (GIII). DC was associated with female gender (p = 0.095, and 0.002 for OR), non-mucinous tumor (p &lt; 0.001, and 0.006 for OR) and absence of rales (p = 0.009) but not with smoking (except for OR, p = 0.024), PS, bronchorrhea, hypoxemia, extra-thoracic metastasis, or Tx presentation. Conclusions: Gefitinib is active and well-tolerated as first-line treatment of non-resectable P-ADC in a Caucasian population, with a 13% OR rate and a 30% DCR. Interestingly, DC was maintained on a long term under G, maybe resulting in improved survival time. [Table: see text]

Clinical Correlation between the Serum Pepsinogen I/II Ratio and Gastric Cancer

Purpose: In order to clarify the carcinogenesis mechanism from chronic atrophic gastritis toward gastric cancer, we measured the pepsinogen I and II and compared their ratio with several clinical findings. Materials and Methods: We measured the preoperative serum pepsinogen I and II by using a radio-immunoassay and compared their ratio with several clinical findings, such as tumor size, mucinous vs non-mucinous tumor, cell differentiation, tumor location, depth of invasion, lymph-node status, Lauren's classification, and peritumoral atrophy in 103 consecutive patients with gastric adenocarcinomas who had received resections at Bundang CHA Hospital during the period from July 2003 to February 2005. Results: There were significant differences in the serum pepsinogen I/II ratio between patients with mucinous vs non-mucinous tumors (n=4 vs 9 and mean pep I/II=1.29 vs. 2.99, p=0.0288), with tumor size more than and less than (n=55 vs. 48 and mean pep I/II=2.64 vs. 3.24, p=0.0491), and with or without peritumoral atrophy (n=94 vs. 9 and mean pep I/II=2.83 vs. 3.89, p=0.0466). In patients with peritomoral atrophy, the pepsinogen I/II ratio was also lower in larger tumors (n=48 vs. 46 and mean pep I/II=2.44 vs. 3.23, p=0.0083). Well-differentiated carcinomas showed significantly lower serum pep I/II ratios than signet-ring-ceil types. There was no correlation between serum pep I/II ratio and tumor location, depth of invasion, lymph-node status, or Lauren's classification Conclusion: We proved the existence of a correlation between serum pepsinogen level and musosal atrophy, but these results are not sufficient for clinical application of serum pepsinogen level as a screening tool for gastric cancer.

Unfavorable expression of pharmacologic markers in mucinous colorectal cancer (CRC)

Abstract Introduction: Patients with mucinous CRC generally have worse prognoses than those with the non-mucinous variety. The reason for this disparity is unclear but may result from a differential response to adjuvant chemotherapy. We examined known molecular markers for response to common chemotherapy in these two histologic subtypes. Methods: Medical records of surgically-treated patients with stage III CRC were reviewed for demographic data and outcome. Twenty-one patients with mucinous and thirty with non-mucinous tumors were matched for age, gender, tumor size, grade and location, and number of lymph node metastases. Total RNA from the tumors and adjacent normal mucosa was isolated and reverse transcribed. Quantitative expression levels of drug pathway genes were determined using TaqMan RT-PCR (5-FU: TYMS, DPYD, ECGF1; oxaliplatin: GSTP1, ERCC1 & 2; irinotecan: ABCB1, ABCG2, CYP3A4, UGT1A1, CES2, TOP1). Results: Mucinous tumors significantly overexpressed both TYMS and GSTP1 relative to non-mucinous tumors and patient-matched normal mucosa. No significant differences in expression of the remaining markers were found. Mean follow-up was 20 months; 17 patients had recurrent disease. Among patients receiving 5-FU, those with mucinous CRC experienced shorter disease-free survival than those with non-mucinous tumors (median DFS 13.8 vs. 46.5 months, p = 0.053). ∗ . Mucinous Non-mucinous Mucosa Tumor Mucosa Tumor TYMS 4.1 ± 0.4 17.7 ± 5.8 ∗† 4.9 ± 0.7 9.6 ± 2.3 ∗ GSTP1 60 ± 9.6 193 ± 40.4 ∗† 51 ± 7.1 139 ± 32.7 ∗ ∗ Denotes p † Denotes p Conclusions: Mucinous tumors overexpressed markers of resistance to 5-FU and oxaliplatin. Additionally, DFS was decreased in patients with mucinous CRC who were given 5-FU. Expression differences in genes influencing chemotherapeutic response may contribute to shorter times to recurrence in patients with mucinous tumors, suggesting that mucin staining should be evaluated in developmental trials for novel CRC treatments.

Mucinous carcinoma of the colon and rectum

The clinicopathologic significance of mucus production by adenocarcinoma of the colon and rectum was analyzed in retrospective study with stage matched non-mucus producing control carcinomas. Mucinous carcinoma of the colon and rectum comprised 132 (15%) of 893 cases of colorectal carcinoma. The rectum was the most common site (33% of cases). While 120 mucinous cancers had a poorer five-year survival than non-mucinous tumors (34% vs. 53%, p less than .005), these had a particularly bad prognosis in the rectum (18% 5 year survival vs. 49% for the non-mucinous tumor controls, p less than .00k). The theoretical basis for this location-dependent behavior is considered. From this study, distinctive clinico-pathologic features emerge. There were seven documented cases of ulcerative colitis and 8 additional patients gave a history of "colitis". An additional five patients had received prior pelvic irradiation. Of particular note was the fact that 31% of mucinous carcinomas were associated with villous adenomas, implying a histogenetic relationship. Moreover, this finding again emphasizes the neoplastic potential of the villous adenoma, especially in the rectum where the development of mucinous carcinoma is particularly ominous.