Powered Stapler and Polyglycolic Acid Sheet for Pancreatic Fistula after Distal Pancreatectomy.

BACKGROUND: Although distal pancreatectomy (DP) is critical for the treatment of pancreatic diseases, it often leads to postoperative pancreatic fistula (POPF), a complication with significant management challenges and health impacts. Despite the use of various techniques, including suturing methods, staplers, and biodegradable materials, the optimal strategy to reduce POPF remains unclear. This study investigated the combined use of powered staplers and polyglycolic acid (PGA) sheets to mitigate POPF. METHODS: We retrospectively analyzed the data of 165 patients who underwent DP at Sapporo Medical University Hospital between January 2013 and August 2023. This study compared the incidence of clinically relevant POPF (CR-POPF) between patients treated without (group O, n=50) and with powered staplers and PGA sheets (group P, n=115). The surgical techniques, patient demographics, and postoperative outcomes were also examined. RESULTS: We found no significant difference in the overall incidence of POPF between the groups. However, group P had a significantly lower incidence of CR-POPF than group O (20.9% vs. 40.0%, p=0.011). Multivariable analysis demonstrated that male sex (odds ratio [OR]: 2.81; 95% confidence interval (CI) [1.26-6.26], p=0.012) and pancreatic thickness over 14mm (OR 2.85; 95%CI [1.17-6.95], p=0.021) were identified as independent risk factors for CR-POPF. The use of powered staplers and PGA sheets (OR 0.38; 95%CI [0.17-0.85], p=0.017) was associated with reduced CR-POPF risk. CONCLUSION: The combined use of powered staplers and PGA sheets can significantly decrease the incidence of CR-POPF in patients with DP.

Prognostic Impact of Human Lymphocyte Antigen (HLA) Class I Expression in Patients With Breast Cancer.

BACKGROUND/AIM: Various biomarkers are utilized in the field of breast cancer. Human lymphocyte antigen (HLA) class I molecules have a critical role in cancer immune surveillance. Therefore, this study aimed to assess the HLA class I expression and analyze the correlation with clinicopathologic factors in breast cancer. PATIENTS AND METHODS: We investigated the clinical pathology archives of 150 consecutive patients with breast cancer who underwent a curative operation at the Sapporo Medical University, Japan, from January 2012 to December 2014. Immunohistochemical staining was used to evaluate HLA class I expression and CD8-positive T cell infiltration. The Pearson χ2 test was used to assess HLA class I expression level and clinicopathological parameters. The Kaplan-Meier method was used to evaluate survival and the log-rank test to analyze the differences between survival curves. RESULTS: Patients with dull/negative HLA class I had significantly poor disease-free survival (DFS) compared with those with positive HLA class I (p=0.0073). Univariate analyses revealed that pT, pN, positive lymphatic invasion, and dull/negative HLA class I were significantly associated with DFS. Multivariate analyses revealed dull/negative HLA class I as an independent poor prognostic factor (hazard ratio=2.75, 95% confidence interval=1.30-5.80, p=0.008). CONCLUSION: HLA class I expression level may have a very sensitive prognostic effect on patients with breast cancer.

Impact of Infrared Indocyanine Green Fluorescence imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis.

BACKGROUND: Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs. METHODS: Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5 mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins. RESULTS: Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074 mm. CONCLUSIONS: We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.

Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1.

Recent studies have shown that transmembrane-type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM-A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM-A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM-A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM-A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM-A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM-A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM-A-targeted therapy ideally combined with LAT1-targeted therapy as a new therapeutic strategy against breast cancer.

Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Eribulin is an immune potentiator in breast cancer that upregulates human leukocyte antigen class I expression via the induction of NOD-like receptor family CARD domain-containing 5.

Eribulin inhibits microtubule polymerization and improves the overall survival of patients with recurrent metastatic breast cancer. A subgroup analysis revealed a low neutrophil to lymphocyte ratio (NLR) (<3) to be a prognostic factor of eribulin treatment. We thus hypothesized that eribulin might be related to the immune response for breast cancer cells and we analyzed the effects of eribulin on the immune system. Immunohistochemical staining revealed that human leukocyte antigen (HLA) class I expression was increased in clinical samples after eribulin treatment. In vitro assays revealed that eribulin treatment increased HLA class I expression in breast cancer line cells. RNA-sequencing demonstrated that eribulin treatment increased the expression of the NOD-like family CARD domain-containing 5 (NLRC5), a master regulator of HLA class I expression. Eribulin treatment increased the NY-ESO-1-specific T-cell receptor (TCR) transduced T (TCR-T) cell response for New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) overexpressed breast cancer cells. The eribulin and TCR-T combined therapy model revealed that eribulin and immunotherapy using TCR-T cells has a synergistic effect. In summary, eribulin increases the expression of HLA class 1 via HLA class 1 transactivatior NLRC5 and eribulin combination with immunotherapy can be effective for the treatment of breast cancer.

Common pathological findings in the heart in COVID-19-related sudden death cases: An autopsy case series.

Background: Cardiomyopathy is a leading cause of sudden out-of-hospital death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Such unexpected COVID-19-related cardiomyopathies are challenging to diagnose as specific pathological findings are not always identified. Case summary: We reported the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies. In one case, death occurred after SARS-CoV-2 infection, while in the other, after COVID-19 vaccination. We found common pathological findings in both hearts: decreased staining intensity with special stains, loss of rhabdomeres, and multivacuolation in cardiomyocytes without inflammatory cell infiltration. The remaining organs showed no findings that could have contributed to the deaths. Conclusion: In cases of sudden death after SARS-CoV-2 infection or COVID-19 vaccination, the decreased staining intensity with special stains may aid the diagnosis of sudden death due to COVID-19-related cardiomyopathy, even when H&E staining shows few findings.

A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

Positional advantages of supine MRI for diagnosis prior to breast­conserving surgery.

The present study aimed to evaluate the rate of positive surgical margins for magnetic resonance imaging (MRI) performed in the supine position prior to breast-conserving surgery (BCS). The rate of positive surgical margins and the clinicopathological factors were examined in consecutive patients with BCS who underwent preoperative MRI performed in the supine position at Sapporo Medical University Hospital (Sapporo, Japan) and related hospitals and clinics between January 2012 and December 2013. Of 1,175 eligible patients, 1,150 were included after excluding 25 patients with either bilateral breast cancer or stage IV disease. Positive margin was defined as no cancer seen on the resected margin. The primary endpoint was the rate of positive surgical margins when preoperative MRI was performed in the supine position and the secondary endpoint was identification of the factors that predict positive margins. Of the 1,150 female patients (median age, 55 years; range, 29-97 years) who underwent BCS for breast cancer following MRI performed in the supine position, 215 (18.8%) had positive margins, which is similar to the rate with MRI in the prone position, and 930 (81.2%) had negative margins. The rate of positive surgical margins in patients of the human epidermal growth factor receptor 2 (HER2) type was significantly higher than that in the non-HER2 type group (6.5 and 2.9%; χ2 P=0.0103). There was no increase in the rate of positive margins in breast cancers with a diameter of >T2. The rate of positive surgical margins following MRI performed in the supine position was 18.8%. Supine MRI appears to be suitable for informing on the extent of resection of breast cancer.

Ischemia-induced intestinal de-epithelization and consequent cholangitis lenta after usage of extracorporeal membrane oxygenation in COVID-19 patients: an autopsy series.

Since its discovery in late 2019, severe acute respiratory syndrome coronavirus 2 has spread around the world, causing millions of deaths due to coronavirus disease 2019 (COVID-19). Numerous clinical and post-mortem investigations of COVID-19 cases have found myriad clinical and pathological manifestations of the disease. In this report, we present three autopsy cases in which, despite weaning from extracorporeal membrane oxygenation (ECMO), extensive intestinal epithelial shedding, probably due to ischemia, was followed by massive watery diarrhea and the spread of infection via the portal vein due to bacterial translocation, which resulted in cholangitis lenta. Thrombophilia was attributed to ECMO usage and COVID-19-related vascular endothelial damage. These cases provide instructive findings showing that the loss of the intestinal barrier may be the underlying cause of severe watery diarrhea and liver failure in COVID-19 patients, especially with ECMO usage.

Elevated expression of endocan in the development of cervical squamous neoplasia of the uterus.

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.

Suppression of the vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer.

Vitamin D is an essential nutrient for the human body not only for the metabolism of calcium but also for homeostasis. Vitamin D contributes to cell fate decisions, including cell proliferation, differentiation and viability. Accumulated epidemiological data suggest a relationship between vitamin D deficiency and carcinogenesis in numerous organs. Furthermore, it is known that the expression of the vitamin D metabolizing enzyme, cytochrome P450 family 24 subtype A1 (CYP24A1), is increased in different types of human malignancy including breast carcinoma. However, the pathological relevance of elevated CYP24A1 expression level requires further clarification. In the present study, it was demonstrated that CYP24A1 promoted the oncogenic property of breast carcinoma cells. Consistent with previous reports, it was demonstrated that the expression of CYP24A1 was elevated in invasive breast carcinoma and significantly decreased the overall survival of patients with invasive breast carcinoma. Importantly, suppression of CYP24A1 expression significantly enhanced cell death sensitivity to two anticancer drugs with pharmacologically different modes of action, cisplatin and gefitinib. The results of the present study suggest the possibility of CYP24A1­inhibiting therapy as a novel therapy in breast cancer with overexpression of CYP24A1.

Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy.

In this review, we discuss the possibility of the vitamin D metabolizing enzyme CYP24A1 being a therapeutic target for various tumors including breast, colorectal and prostate tumors. Given the pleiotropic cellular activity of vitamin D, its deficiency impairs its physiological function in target cells and results in various pathologies including cancer. In addition, accumulated data have shown that elevated expression of CYP24A1 promotes carcinogenesis in various cancer subtypes by decreasing the bioavailability of vitamin D metabolites. Thus, we propose the potential feasibility of vitamin D metabolism-blocking therapy in various types of human malignancies that express constitutive CYP24A1.

Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections.

Invasive pulmonary aspergillosis (IPA) is one of the most frequent forms of invasive fungal infections (IFI); however, it is often difficult to identify the pathogenic fungal species and to select appropriate treatments for patients with IFI including IPA. Here, we describe the detailed pathophysiology of an autopsy case of severe respiratory failure due to IPA with candidiasis. The patient developed severe respiratory failure after influenza infection and died, and the autopsy revealed a mixed disease of IPA with candidiasis. In this study, in addition to the routine pathological examination, we further examined formalin-fixed paraffin-embedded (FFPE) tissues by scanning electron microscopy (SEM) and partial genomic DNA sequencing. Although optical microscopy alone was insufficient to identify the pathogenic organisms, SEM clearly depicted the characteristic morphology of Aspergillus sp. and Candida sp. as closely overlapping in a nested fashion, providing evidence of mixed infection of both fungal species in a focal site. The technique using FFPE tissue in combination with ultrastructural observation by SEM, elemental analysis by SEM-EDX, and DNA sequencing is promising for analyzing the pathophysiology of IFI.

Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy.

Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives. CYP26 enzymes play similar but separate roles in limiting the consequences of fluctuations in nutritional vitamin A. Recently, we found that RA depletion caused by expression of CYP26A1 promotes malignant behaviors of tumor cells derived from various tissues, implicating CYP26A1 as a candidate oncogene. We also showed that the expression levels of CYP26 enzymes are elevated in various types of cancer. We have provided evidence for oncogenic and cell survival properties of CYP26 enzymes, indicating that these molecules are possible therapeutic targets for CYP26-expressing malignancies.

Additional effect of anthracycline in preoperative chemotherapy with a sequential anthracycline­containing regimen preceded by pertuzumab, trastuzumab and docetaxel combination therapy.

The proper use of anthracycline-containing regimens in combination with anti-HER2-targeted therapy in a neoadjuvant setting for patients with HER2-positive breast cancer has not been resolved. Regimens preceded by anthracyclines have become the standard of care, and although the order has no significant impact on HER2-negative breast cancer, it is inconclusive as to whether a taxane-first sequence would have a similar effect on HER2-positive breast cancer. The present study aimed to investigate the benefit of a taxane-first sequence and of adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab and docetaxel (PTD). The present single-center prospective observational study was performed to investigate PTD followed by AC, and aimed to clarify the cCR rate after PTD alone and the pathological clinical response (pCR) rate after subsequent AC in patients without cCR after PTD alone. A total 24 patients were analyzed; of these, 14 achieved pCR (pCR rate, 58.3%). While four of 14 patients (28.6%) in the intention-to-treat population achieved pCR, nine of 14 patients (64.3%) achieved pCR with AC but not cCR after PTD. The median tumor reduction rate after four cycles of PTD was 58.9% (range, 20.8-100%) in all 24 patients, whereas the reduction rate after PTD-AC was 76.9% (range, 31.1-100%). Cardiac serious adverse events occurred in three patients (12.5%). In conclusion, a high pCR rate was observed for the taxane-first sequence. Patients were highly responsive to PTD, but some cases achieved additional antitumor effects after AC, which resulted in pCR without cCR after PTD alone. Since cardiotoxicity remains a significant problem, a higher risk-benefit treatment strategy is required to aim for AC omission. Trial registration number: UMIN000046338, name of registry: UMIN-CTR, date of registration: December 10, 2021.

COVID-19-associated disseminated mucormycosis: An autopsy case report.

BACKGROUND: Reports of mucormycosis, an infectious disease that commonly affects immunocompromised individuals, have increased during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis. Our report documents a case of disseminated mucormycosis after COVID-19 infection. This is a rare pathological autopsy report on COVID-19-associated mucormycosis. CASE SUMMARY: A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia. During treatment for acute respiratory distress syndrome, he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis. The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure, which led to death. An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection, which led to the necrosis of multiple infected organs. CONCLUSION: Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

Disseminated mucormycosis in a patient with severe COVID-19 on venovenous extracorporeal membrane oxygenation: A case report.

Background: Since the global outbreak of coronavirus disease 2019 (COVID-19), there have been several reports of mucormycosis as a secondary complication. However, the disseminated type of mucormycosis is extremely rare. Case: A 58-year-old male patient with COVID-19 started receiving venovenous extracorporeal membrane oxygenation because of severe respiratory failure. During hospitalization, intra-abdominal hemorrhage occurred and an emergency laparotomy was performed. Subsequently, the patient suffered septic shock, and part of the small intestines and the abdominal wall became necrotic. Finally, the patient died. At autopsy, he was diagnosed with disseminated mucormycosis. Conclusion: Disseminated mucormycosis should be considered in patients with COVID-19 with refractory sepsis unresponsive to broad-spectrum antimicrobial therapy.

Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin-6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma (ADC) and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell-cell adhesion-related proteins and drug metabolism-associated proteins (aldo-keto reductase [AKR] family proteins) were significantly increased in CLDN6-overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell-cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical ADC, possibly due to increased cell-cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6-targeting therapy, against cervical ADC.